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

This study has been completed.
Sponsor:
Collaborator:
University of Copenhagen
Information provided by (Responsible Party):
Filip Krag Knop, University Hospital, Gentofte, Copenhagen
ClinicalTrials.gov Identifier:
NCT01656057
First received: July 31, 2012
Last updated: July 10, 2015
Last verified: July 2015
  Purpose

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.


Condition Intervention
To Assess the Impact of Bile Acids on Human Glukagon-like-peptide-1 Secretion
Drug: Acetaminophen
Drug: Metformin
Drug: Colesevelam
Other: Cholecystokinin-8
Other: Saline

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
Official Title: The Impact of Gall Bladder Emptying and Bile Acids on the Human GLP-1-secretion

Resource links provided by NLM:


Further study details as provided by University Hospital, Gentofte, Copenhagen:

Primary Outcome Measures:
  • GLP-1 response as incremental area under curve (iAUC) [ Time Frame: -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Insulin [ Time Frame: -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240 ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • c-peptide [ Time Frame: -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240 ] [ Designated as safety issue: No ]
  • glucagon [ Time Frame: -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240 ] [ Designated as safety issue: No ]
  • Glucagon-Like Peptide-2 [ Time Frame: -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240 ] [ Designated as safety issue: No ]
  • Peptide YY [ Time Frame: -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240 ] [ Designated as safety issue: No ]
  • Oxyntomodulin [ Time Frame: -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240 ] [ Designated as safety issue: No ]
  • Glucose-Dependent Insulinotropic Peptide [ Time Frame: -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240 ] [ Designated as safety issue: No ]
  • Bile acids [ Time Frame: -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240 ] [ Designated as safety issue: No ]
  • Gastrin [ Time Frame: -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240 ] [ Designated as safety issue: No ]
  • CCK [ Time Frame: -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240 ] [ Designated as safety issue: No ]
  • Gall bladder emptying assessed ultrasonically [ Time Frame: -30, -15, 20, 40, 60, 90, 120, 150, 180 ] [ Designated as safety issue: No ]
  • Resting energy expenditure [ Time Frame: -10, 50, 210 ] [ Designated as safety issue: No ]
  • Estimation of satiety via visual analogue scale [ Time Frame: 0, 30, 60, 90, 120, 150, 180, 240 ] [ Designated as safety issue: No ]

Enrollment: 10
Study Start Date: July 2012
Study Completion Date: April 2014
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Acetaminophen+saline
Acetaminophen tablet 1500 mg via nasogastric tube + i.v. saline
Drug: Acetaminophen
Acetaminophen dissolved in 50 ml of water
Other Name: Paracetamol
Other: Saline
iv. saline infusion 40 ml/hour for the first 60 minutes
Experimental: Acetaminophen+CCK
Acetaminophen tablet 1500 mg via nasogastric tube + iv. CCK-8, 24 pmol/kg/hour
Drug: Acetaminophen
Acetaminophen dissolved in 50 ml of water
Other Name: Paracetamol
Other: Cholecystokinin-8
iv. infusion of CCK-8, 24 pmol/kg/hour for the first 60 minutes
Other Name: CCK-8
Experimental: Metformin+saline
Metformin tablet 1500 mg + Acetaminophen tablet 1500 mg via nasogastric tube + i.v. saline
Drug: Acetaminophen
Acetaminophen dissolved in 50 ml of water
Other Name: Paracetamol
Drug: Metformin
Metformin + acetaminophen dissolved in 50 ml of water
Other: Saline
iv. saline infusion 40 ml/hour for the first 60 minutes
Experimental: Metformin+CCK
Metformin tablet 1500 mg + Acetaminophen tablet 1500 mg via nasogastric tube + iv. CCK-8, 24 pmol/kg/hour
Drug: Acetaminophen
Acetaminophen dissolved in 50 ml of water
Other Name: Paracetamol
Drug: Metformin
Metformin + acetaminophen dissolved in 50 ml of water
Other: Cholecystokinin-8
iv. infusion of CCK-8, 24 pmol/kg/hour for the first 60 minutes
Other Name: CCK-8
Experimental: Colesevelam+saline
Colesevelam tablet 3750 mg + Acetaminophen tablet 1500 mg via nasogastric tube + iv. saline
Drug: Acetaminophen
Acetaminophen dissolved in 50 ml of water
Other Name: Paracetamol
Drug: Colesevelam
Colesevelam + acetaminophen dissolved in 50 ml of water
Other: Saline
iv. saline infusion 40 ml/hour for the first 60 minutes
Experimental: Colesevelam+CCK
Colesevelam tablet 3750 mg + Acetaminophen tablet 1500 mg via nasogastric tube + iv. CCK-8, 24 pmol/kg/hour
Drug: Acetaminophen
Acetaminophen dissolved in 50 ml of water
Other Name: Paracetamol
Drug: Colesevelam
Colesevelam + acetaminophen dissolved in 50 ml of water
Other: Cholecystokinin-8
iv. infusion of CCK-8, 24 pmol/kg/hour for the first 60 minutes
Other Name: CCK-8

  Eligibility

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01656057

Locations
Denmark
University Hospital of Copenhagen, Gentofte Hospital, Diabetic Research Division
Copenhagen, Hellerup, Denmark, 2900
Sponsors and Collaborators
Filip Krag Knop
University of Copenhagen
Investigators
Principal Investigator: Ulrich Rohde, MD Diabetic Research Division, Department of Internal Medicine, University Hospital of Copenhagen, Gentofte Hospital
  More Information

No publications provided

Responsible Party: Filip Krag Knop, MD, Ph.D., University Hospital, Gentofte, Copenhagen
ClinicalTrials.gov Identifier: NCT01656057     History of Changes
Other Study ID Numbers: GALINKUR
Study First Received: July 31, 2012
Last Updated: July 10, 2015
Health Authority: Denmark: Danish Dataprotection Agency
Denmark: The Regional Committee on Biomedical Research Ethics

Keywords provided by University Hospital, Gentofte, Copenhagen:
Bile acids
Gall bladder emptying
Human
Glucagon like peptide 1
GLP-1

Additional relevant MeSH terms:
Acetaminophen
Cholecystokinin
Colesevelam
Metformin
Analgesics
Analgesics, Non-Narcotic
Anticholesteremic Agents
Antimetabolites
Antipyretics
Central Nervous System Agents
Cholagogues and Choleretics
Gastrointestinal Agents
Hypoglycemic Agents
Hypolipidemic Agents
Lipid Regulating Agents
Molecular Mechanisms of Pharmacological Action
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 27, 2015