Effect of Bile Acids on GLP-1 Secretion

Not Applicable

Completed

• Conditions: Type 2 Diabetes; Obesity
• Interventions: Drug: Colesevelam 3750 mg + chenodeoxycholic acid 1250 mg; Other: saline; Drug: Colesevelam; Drug: Chenodeoxycholic Acid

• Registration Number: NCT01666223
• Lead Sponsor: University Hospital, Gentofte, Copenhagen

Brief Summary

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.

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 Timeline

• Study First Submitted: 2012-07-11
• Study First Submitted QC: 2012-08-15
• Study First Posted: 2012-08-16
• Study Start: 2012-11
• Primary Completion: 2013-06
• Study Completion: 2013-06
• Status Verified: 2013-12
• Last Update Submitted: 2013-12-21
• Last Update Posted: 2013-12-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Colesevelam + chenodeoxycholic acid	Colesevelam 3750 mg + chenodeoxycholic acid 1250 mg	-
Placebo	saline	-
Colesevelam	Colesevelam	-
Chenodeoxycholic acid	Chenodeoxycholic Acid	-

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Change in peptide YY (PYY)	At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes
Change in oxyntomodulin	At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes
Change in bile acids	At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes
Change in gastrin	At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes
Change in CCK	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	At baseline, and 30, 60, 90, 120 and 180 minutes	Evaluated by Visual Analog Scale (VAS)
Change in gallbladder volume	-30, 0 (baseline), 30, 60, 120 og 180 minutes	Evaluated by ultrasound
Change in basal metabolic rate	At -30, 60 og 150 minutes	Evaluated by indirect calorimetry
Change in bile acid composition	At -30, 0, 30, 60, 120 og 180 minutes	Evaluated by duodenal aspiration
Change in insulin	At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes
Change in C-peptide	At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes
Change in glucagon	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)	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)	At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes

Trial Locations

Locations (1)

Diabetes Research Division, Department of Internal Medicine, Gentofte Hospital, University of Copenhagen; 🇩🇰 Hellerup, Copenhagen, Denmark