The Impact of Gall Bladder Emptying and Bile Acids on the Human GLP-1-secretion
1 other identifier
interventional
10
1 country
1
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for not_applicable
Started Jul 2012
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
July 1, 2012
CompletedFirst Submitted
Initial submission to the registry
July 31, 2012
CompletedFirst Posted
Study publicly available on registry
August 2, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 1, 2013
CompletedStudy Completion
Last participant's last visit for all outcomes
April 1, 2014
CompletedJuly 14, 2015
July 1, 2015
1.3 years
July 31, 2012
July 10, 2015
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
GLP-1 response as incremental area under curve (iAUC)
-30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240
Secondary Outcomes (1)
Insulin
-30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240
Other Outcomes (12)
c-peptide
-30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240
glucagon
-30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240
Glucagon-Like Peptide-2
-30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240
- +9 more other outcomes
Study Arms (6)
Acetaminophen+saline
EXPERIMENTALAcetaminophen tablet 1500 mg via nasogastric tube + i.v. saline
Acetaminophen+CCK
EXPERIMENTALAcetaminophen tablet 1500 mg via nasogastric tube + iv. CCK-8, 24 pmol/kg/hour
Metformin+saline
EXPERIMENTALMetformin tablet 1500 mg + Acetaminophen tablet 1500 mg via nasogastric tube + i.v. saline
Metformin+CCK
EXPERIMENTALMetformin tablet 1500 mg + Acetaminophen tablet 1500 mg via nasogastric tube + iv. CCK-8, 24 pmol/kg/hour
Colesevelam+saline
EXPERIMENTALColesevelam tablet 3750 mg + Acetaminophen tablet 1500 mg via nasogastric tube + iv. saline
Colesevelam+CCK
EXPERIMENTALColesevelam tablet 3750 mg + Acetaminophen tablet 1500 mg via nasogastric tube + iv. CCK-8, 24 pmol/kg/hour
Interventions
Acetaminophen dissolved in 50 ml of water
Colesevelam + acetaminophen dissolved in 50 ml of water
iv. infusion of CCK-8, 24 pmol/kg/hour for the first 60 minutes
iv. saline infusion 40 ml/hour for the first 60 minutes
Eligibility Criteria
You may qualify if:
- HbA1c \< 6,0%
- Not anaemic
- Written informed consent
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Filip Krag Knoplead
- University of Copenhagencollaborator
Study Sites (1)
University Hospital of Copenhagen, Gentofte Hospital, Diabetic Research Division
Copenhagen, Hellerup, 2900, Denmark
Related Publications (1)
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.
PMID: 27003305DERIVED
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Ulrich Rohde, MD
Diabetic Research Division, Department of Internal Medicine, University Hospital of Copenhagen, Gentofte Hospital
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- BASIC SCIENCE
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- MD, Ph.D.
Study Record Dates
First Submitted
July 31, 2012
First Posted
August 2, 2012
Study Start
July 1, 2012
Primary Completion
October 1, 2013
Study Completion
April 1, 2014
Last Updated
July 14, 2015
Record last verified: 2015-07