Effect of Bile Acids on GLP-1 Secretion

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Morten Hansen, University Hospital, Gentofte, Copenhagen
ClinicalTrials.gov Identifier:
NCT01666223
First received: July 11, 2012
Last updated: December 21, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention
Type 2 Diabetes
Obesity
Drug: Colesevelam
Drug: Chenodeoxycholic Acid
Other: saline
Drug: Colesevelam 3750 mg + chenodeoxycholic acid 1250 mg

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Effect of Bile Acids in the Gut on GLP-1 Secretion in Healthy Subjects and Patients With Type 2 Diabetes

Resource links provided by NLM:


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

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in insulin [ Time Frame: At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Change in glucagon [ Time Frame: At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Change in oxyntomodulin [ Time Frame: At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Change in gastrin [ Time Frame: At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes ] [ Designated as safety issue: No ]
  • Change in CCK [ Time Frame: At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes ] [ Designated as safety issue: No ]
  • Change in appetite, satiety and prospective food consumption [ Time Frame: At baseline, and 30, 60, 90, 120 and 180 minutes ] [ Designated as safety issue: No ]
    Evaluated by Visual Analog Scale (VAS)

  • Change in gallbladder volume [ Time Frame: -30, 0 (baseline), 30, 60, 120 og 180 minutes ] [ Designated as safety issue: No ]
    Evaluated by ultrasound

  • Change in basal metabolic rate [ Time Frame: At -30, 60 og 150 minutes ] [ Designated as safety issue: No ]
    Evaluated by indirect calorimetry

  • Change in bile acid composition [ Time Frame: At -30, 0, 30, 60, 120 og 180 minutes ] [ Designated as safety issue: No ]
    Evaluated by duodenal aspiration


Enrollment: 20
Study Start Date: November 2012
Study Completion Date: June 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Experimental: Placebo Other: saline
100 ml saline

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  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: NCT01666223

Locations
Denmark
Diabetes Research Division, Department of Internal Medicine, Gentofte Hospital, University of Copenhagen
Hellerup, Copenhagen, Denmark
Sponsors and Collaborators
University Hospital, Gentofte, Copenhagen
Investigators
Principal Investigator: Morten Hansen, MD Diabetes Research Division, Department of Internal Medicine, Gentofte Hospital, University of Copenhagen
  More Information

Publications:
Responsible Party: Morten Hansen, MD, PhD Student, University Hospital, Gentofte, Copenhagen
ClinicalTrials.gov Identifier: NCT01666223     History of Changes
Other Study ID Numbers: H-1-2012-049
Study First Received: July 11, 2012
Last Updated: December 21, 2013
Health Authority: Denmark: The Danish National Committee on Biomedical Research Ethics

Keywords provided by University Hospital, Gentofte, Copenhagen:
Type 2 diabetes
GLP-1
Bile acid
TGR-5

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Obesity
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Bile Acids and Salts
Chenodeoxycholic Acid
Colesevelam
Gastrointestinal Agents
Therapeutic Uses
Pharmacologic Actions
Cathartics
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents

ClinicalTrials.gov processed this record on August 20, 2014