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

July 10, 2015 updated by: Filip Krag Knop

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

10

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
      • Copenhagen, Hellerup, Denmark, 2900
        • University Hospital of Copenhagen, Gentofte Hospital, Diabetic Research Division

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 40 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Male

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: BASIC_SCIENCE
  • Allocation: RANDOMIZED
  • Interventional Model: SINGLE_GROUP
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Acetaminophen+saline
Acetaminophen tablet 1500 mg via nasogastric tube + i.v. saline
Drug: Acetaminophen
Acetaminophen dissolved in 50 ml of water
Other Names:
  • 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 Names:
  • Paracetamol
Other: Cholecystokinin-8
iv. infusion of CCK-8, 24 pmol/kg/hour for the first 60 minutes
Other Names:
  • 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 Names:
  • Paracetamol
Other: Saline
iv. saline infusion 40 ml/hour for the first 60 minutes
Drug: Metformin
Metformin + acetaminophen dissolved in 50 ml of water
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 Names:
  • Paracetamol
Other: Cholecystokinin-8
iv. infusion of CCK-8, 24 pmol/kg/hour for the first 60 minutes
Other Names:
  • CCK-8
Drug: Metformin
Metformin + acetaminophen dissolved in 50 ml of water
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 Names:
  • Paracetamol
Other: Saline
iv. saline infusion 40 ml/hour for the first 60 minutes
Drug: Colesevelam
Colesevelam + acetaminophen dissolved in 50 ml of water
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 Names:
  • Paracetamol
Other: Cholecystokinin-8
iv. infusion of CCK-8, 24 pmol/kg/hour for the first 60 minutes
Other Names:
  • CCK-8
Drug: Colesevelam
Colesevelam + acetaminophen dissolved in 50 ml of water

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
-30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240

Secondary Outcome Measures

Outcome Measure
Time Frame
Insulin
Time Frame: -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240
-30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240

Other Outcome Measures

Outcome Measure
Time Frame
c-peptide
Time Frame: -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240
-30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240
glucagon
Time Frame: -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240
-30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240
Glucagon-Like Peptide-2
Time Frame: -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240
-30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240
Peptide YY
Time Frame: -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240
-30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240
Oxyntomodulin
Time Frame: -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240
-30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240
Glucose-Dependent Insulinotropic Peptide
Time Frame: -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240
-30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240
Bile acids
Time Frame: -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240
-30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240
Gastrin
Time Frame: -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240
-30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240
CCK
Time Frame: -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240
-30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240
Gall bladder emptying assessed ultrasonically
Time Frame: -30, -15, 20, 40, 60, 90, 120, 150, 180
-30, -15, 20, 40, 60, 90, 120, 150, 180
Resting energy expenditure
Time Frame: -10, 50, 210
-10, 50, 210
Estimation of satiety via visual analogue scale
Time Frame: 0, 30, 60, 90, 120, 150, 180, 240
0, 30, 60, 90, 120, 150, 180, 240

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Filip Krag Knop

Collaborators

University of Copenhagen

Investigators

  • Principal Investigator: Ulrich Rohde, MD, Diabetic Research Division, Department of Internal Medicine, University Hospital of Copenhagen, Gentofte Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2012

Primary Completion (ACTUAL)

October 1, 2013

Study Completion (ACTUAL)

April 1, 2014

Study Registration Dates

First Submitted

July 31, 2012

First Submitted That Met QC Criteria

July 31, 2012

First Posted (ESTIMATE)

August 2, 2012

Study Record Updates

Last Update Posted (ESTIMATE)

July 14, 2015

Last Update Submitted That Met QC Criteria

July 10, 2015

Last Verified

July 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GALINKUR

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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