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

NCT ID: NCT01656057

Last Updated: 2015-07-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-07-31
• Study Completion Date: 2014-04-30

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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

Acetaminophen+saline

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

Group Type: EXPERIMENTAL

Acetaminophen

Intervention Type: DRUG

Acetaminophen dissolved in 50 ml of water

Saline

Intervention Type: OTHER

iv. saline infusion 40 ml/hour for the first 60 minutes

Acetaminophen+CCK

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

Group Type: EXPERIMENTAL

Acetaminophen

Intervention Type: DRUG

Acetaminophen dissolved in 50 ml of water

Cholecystokinin-8

Intervention Type: OTHER

iv. infusion of CCK-8, 24 pmol/kg/hour for the first 60 minutes

Metformin+saline

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

Group Type: EXPERIMENTAL

Acetaminophen

Intervention Type: DRUG

Acetaminophen dissolved in 50 ml of water

Metformin

Intervention Type: DRUG

Metformin + acetaminophen dissolved in 50 ml of water

Saline

Intervention Type: OTHER

iv. saline infusion 40 ml/hour for the first 60 minutes

Metformin+CCK

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

Group Type: EXPERIMENTAL

Acetaminophen

Intervention Type: DRUG

Acetaminophen dissolved in 50 ml of water

Metformin

Intervention Type: DRUG

Metformin + acetaminophen dissolved in 50 ml of water

Cholecystokinin-8

Intervention Type: OTHER

iv. infusion of CCK-8, 24 pmol/kg/hour for the first 60 minutes

Colesevelam+saline

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

Group Type: EXPERIMENTAL

Acetaminophen

Intervention Type: DRUG

Acetaminophen dissolved in 50 ml of water

Colesevelam

Intervention Type: DRUG

Colesevelam + acetaminophen dissolved in 50 ml of water

Saline

Intervention Type: OTHER

iv. saline infusion 40 ml/hour for the first 60 minutes

Colesevelam+CCK

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

Group Type: EXPERIMENTAL

Acetaminophen

Intervention Type: DRUG

Acetaminophen dissolved in 50 ml of water

Colesevelam

Intervention Type: DRUG

Colesevelam + acetaminophen dissolved in 50 ml of water

Cholecystokinin-8

Intervention Type: OTHER

iv. infusion of CCK-8, 24 pmol/kg/hour for the first 60 minutes

Interventions

Acetaminophen

Acetaminophen dissolved in 50 ml of water

Intervention Type: DRUG

Metformin

Metformin + acetaminophen dissolved in 50 ml of water

Intervention Type: DRUG

Colesevelam

Colesevelam + acetaminophen dissolved in 50 ml of water

Intervention Type: DRUG

Cholecystokinin-8

iv. infusion of CCK-8, 24 pmol/kg/hour for the first 60 minutes

Intervention Type: OTHER

Saline

iv. saline infusion 40 ml/hour for the first 60 minutes

Intervention Type: OTHER

Other Intervention Names

Paracetamol; CCK-8

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

University of Copenhagen

OTHER

Sponsor Role: collaborator

Filip Krag Knop

OTHER

Sponsor Role: lead

Responsible Party

Filip Krag Knop

MD, Ph.D.

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Ulrich Rohde, MD

Role: PRINCIPAL_INVESTIGATOR

Diabetic Research Division, Department of Internal Medicine, University Hospital of Copenhagen, Gentofte Hospital

Locations

University Hospital of Copenhagen, Gentofte Hospital, Diabetic Research Division

Copenhagen, Hellerup, , Denmark

Countries

Denmark

References

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.

Reference Type: DERIVED

PMID: 27003305 (View on PubMed)

Other Identifiers

GALINKUR

Identifier Type: -

Identifier Source: org_study_id