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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified July 2012 by University Hospital, Gentofte, Copenhagen.
Recruitment status was  Recruiting
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: NA
Last verified: July 2012
History: No changes posted
  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 energi 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 GLP-1 in respons 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 the maintainance of a 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 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: Colesevelam

Study Type: Interventional
Study Design: 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 ] [ Designated as safety issue: No ]

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

Other Outcome Measures:
  • c-peptide [ Time Frame: -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 180 ] [ Designated as safety issue: No ]
  • glucagon [ Time Frame: -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 180 ] [ Designated as safety issue: No ]
  • GLP-2 [ Time Frame: -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 180 ] [ Designated as safety issue: No ]
  • PYY [ Time Frame: -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 180 ] [ Designated as safety issue: No ]
  • Oxyntomodulin [ Time Frame: -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 180 ] [ Designated as safety issue: No ]
  • GIP [ Time Frame: -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 180 ] [ Designated as safety issue: No ]
  • Bile acids [ Time Frame: -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 180 ] [ Designated as safety issue: No ]
  • Gastrin [ Time Frame: -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 180 ] [ Designated as safety issue: No ]
  • CCK [ Time Frame: -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 180 ] [ Designated as safety issue: No ]
  • Gall bladder emptying assessed ultrasonically [ Time Frame: 0, 30, 60, 90 ] [ Designated as safety issue: No ]
  • Resting energy expenditure [ Time Frame: -10, 50, 170 ] [ Designated as safety issue: No ]
  • Estimation of satiety via visual analogue scale [ Time Frame: 0, 30, 60, 90, 120, 150, 180 ] [ Designated as safety issue: No ]

Estimated Enrollment: 10
Study Start Date: July 2012
Estimated Study Completion Date: February 2013
Estimated Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Colesevelam
    Day 1: 1 ml isotone sodium cloride IV infusion Day 2: 24 pmol human CCK/kg/hour IV infusion Day 3: 1 ml isotone sodium cloride IV infusion + orally 3,75 grams of colesevelam Day 4: 24 pmol human CCK/kg/hour IV infusion + orally 3,75 grams of colesevelam Day 5: 1 ml isotone sodium cloride IV infusion + orally 1,5 grams of metformin Day 6: 24 pmol human CCK/kg/hour IV infusion + orally 1,5 grams of metformin
    Other Name: Metformin
  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 glucos > 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 Recruiting
Copenhagen, Hellerup, Denmark, 2900
Contact: Filip Krag Knop, MD, Ph.D.    (+45) 39778132    filipknop@dadlnet.dk   
Contact: Ulrich Rohde, MD         
Sponsors and Collaborators
Filip Krag Knop
University of Copenhagen
  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 31, 2012
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:
Colesevelam
Anticholesteremic Agents
Antimetabolites
Hypolipidemic Agents
Lipid Regulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 19, 2014