Effect of Bile Acids on GLP-1 Secretion

December 21, 2013 updated by: Morten Hansen, University Hospital, Gentofte, Copenhagen

Effect of Bile Acids in the Gut on GLP-1 Secretion in Healthy Subjects and Patients With Type 2 Diabetes

The purpose of this study is to describe the physiological, pathophysiological and potentially therapeutic implications of bile-induced glucagon-like peptide-1 (GLP-1) secretion in human glucose homeostasis.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The investigators hypothesize that even modest increments in endogenous GLP-1 secretion will elicit important antidiabetic effects of GLP-1. To evaluate whether bile acids have such effects, the investigators plan to perform intraduodenal infusion of two different bile acids and placebo.

Study Type

Interventional

Enrollment (Actual)

20

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, Copenhagen, Denmark
        • Diabetes Research Division, Department of Internal Medicine, Gentofte Hospital, University of Copenhagen

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 and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Patients with type 2 diabetes

Inclusion Criteria:

  • danish caucasian ethnicity
  • normal haemoglobin
  • BMI > 25 kg/m2
  • HbA1c < 9%
  • informed consent

Exclusion Criteria:

  • liver disease(ALT and AST > upper reference limit)
  • gastrointestinal disease
  • liver and biliary tract disease
  • nephropathy (serum creatinine > 150 μM, and/or albuminuria)
  • treatment with insulin, glp-1 analogues and/ or DPP-4 inhibitors
  • treatment with medicine that can not be paused for 12 hours
  • previous abdominal surgery eg. cholecystectomy
  • BMI < 18,5 kg/m2 or > 35 kg/m2

Healthy Volunteers

Inclusion Criteria:

  • danish caucasian ethnicity
  • normal haemoglobin
  • HbA1c < 6,0 (American Diabetes Association guidelines)
  • informed consent

Exclusion Criteria:

  • liver disease(ALT and AST > upper reference limit)
  • gastrointestinal disease
  • liver and biliary tract disease
  • nephropathy (serum creatinine > 150 μM, and/or albuminuria)
  • treatment with medicine that can not be paused for 12 hours
  • previous abdominal surgery eg. cholecystectomy
  • BMI < 18,5 kg/m2 or > 35 kg/m2
  • first degree relatives diagnosed with diabetes
  • previously diagnosed with diabetes, or treated with antidiabetic agents

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: CROSSOVER
  • Masking: TRIPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Placebo
Other: saline
100 ml saline
EXPERIMENTAL: Colesevelam
Drug: Colesevelam
Colesevelam 3750 mg dissolved in 100 ml saline, administered in a feeding tube at time = 0.
EXPERIMENTAL: Chenodeoxycholic acid
Drug: Chenodeoxycholic Acid
1.250 mg dissolved in 100 ml saline, administered in a feeding tube at time = 0.
EXPERIMENTAL: Colesevelam + chenodeoxycholic acid
Drug: Colesevelam 3750 mg + chenodeoxycholic acid 1250 mg
Colesevelam and chenodeoxycholic acid dissolved in 100 ml saline, administered in a duodenal tube at time = 0.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Change in GLP-1
Time Frame: At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes
At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in insulin
Time Frame: At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes
At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes
Change in C-peptide
Time Frame: At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes
At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes
Change in glucagon
Time Frame: At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes
At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes
Change in glucagon-like-peptide 2 (GLP-2)
Time Frame: At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes
At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes
Change in glucose-dependent insulinotropic polypeptide (GIP)
Time Frame: At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes
At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes
Change in peptide YY (PYY)
Time Frame: At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes
At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes
Change in oxyntomodulin
Time Frame: At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes
At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes
Change in bile acids
Time Frame: At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes
At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes
Change in gastrin
Time Frame: At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes
At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes
Change in CCK
Time Frame: At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes
At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes
Change in appetite, satiety and prospective food consumption
Time Frame: At baseline, and 30, 60, 90, 120 and 180 minutes
Evaluated by Visual Analog Scale (VAS)
At baseline, and 30, 60, 90, 120 and 180 minutes
Change in gallbladder volume
Time Frame: -30, 0 (baseline), 30, 60, 120 og 180 minutes
Evaluated by ultrasound
-30, 0 (baseline), 30, 60, 120 og 180 minutes
Change in basal metabolic rate
Time Frame: At -30, 60 og 150 minutes
Evaluated by indirect calorimetry
At -30, 60 og 150 minutes
Change in bile acid composition
Time Frame: At -30, 0, 30, 60, 120 og 180 minutes
Evaluated by duodenal aspiration
At -30, 0, 30, 60, 120 og 180 minutes

Collaborators and Investigators

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

Sponsor

University Hospital, Gentofte, Copenhagen

Investigators

  • Principal Investigator: Morten Hansen, MD, Diabetes Research Division, Department of Internal Medicine, Gentofte Hospital, University of Copenhagen

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

November 1, 2012

Primary Completion (ACTUAL)

June 1, 2013

Study Completion (ACTUAL)

June 1, 2013

Study Registration Dates

First Submitted

July 11, 2012

First Submitted That Met QC Criteria

August 15, 2012

First Posted (ESTIMATE)

August 16, 2012

Study Record Updates

Last Update Posted (ESTIMATE)

December 24, 2013

Last Update Submitted That Met QC Criteria

December 21, 2013

Last Verified

December 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • H-1-2012-049

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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