The Impact of Gall Bladder Emptying and Bile Acids on the Human GLP-1-secretion

Filip Krag Knop

Status: Completed

Conditions: To Assess the Impact of Bile Acids on Human Glukagon-like-peptide-1 Secretion

Treatments: Other: Cholecystokinin-8; Drug: Colesevelam; Drug: Metformin; Other: Saline; Drug: Acetaminophen

Study type: Interventional

Funder types: Other

Identifiers

NCT01656057

GALINKUR

Details and patient eligibility

About

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.

Enrollment: 10 patients

Sex: Male

Ages: 18 to 40 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Single Group Assignment

Masking: Double Blind

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10 participants in 6 patient groups

Acetaminophen+saline

Experimental group

Description:

Acetaminophen tablet 1500 mg via nasogastric tube + i.v. saline

Treatment:

Drug: Acetaminophen

Other: Saline

Acetaminophen+CCK

Experimental group

Description:

Acetaminophen tablet 1500 mg via nasogastric tube + iv. CCK-8, 24 pmol/kg/hour

Treatment:

Drug: Acetaminophen

Other: Cholecystokinin-8

Metformin+saline

Experimental group

Description:

Metformin tablet 1500 mg + Acetaminophen tablet 1500 mg via nasogastric tube + i.v. saline

Treatment:

Drug: Acetaminophen

Drug: Metformin

Other: Saline

Metformin+CCK

Experimental group

Description:

Metformin tablet 1500 mg + Acetaminophen tablet 1500 mg via nasogastric tube + iv. CCK-8, 24 pmol/kg/hour

Treatment:

Drug: Acetaminophen

Drug: Metformin

Other: Cholecystokinin-8

Colesevelam+saline

Experimental group

Description:

Colesevelam tablet 3750 mg + Acetaminophen tablet 1500 mg via nasogastric tube + iv. saline

Treatment:

Drug: Colesevelam

Drug: Acetaminophen

Other: Saline

Colesevelam+CCK

Experimental group

Description:

Colesevelam tablet 3750 mg + Acetaminophen tablet 1500 mg via nasogastric tube + iv. CCK-8, 24 pmol/kg/hour

Treatment:

Drug: Colesevelam

Drug: Acetaminophen

Other: Cholecystokinin-8