Back to resultsEffect of Bile Acids on GLP-1 Secretion
Primary Purpose
Type 2 Diabetes, Obesity
Status
Completed
Phase
Not Applicable
Locations
Denmark
Study Type
Interventional
Intervention
Colesevelam
Chenodeoxycholic Acid
saline
Colesevelam 3750 mg + chenodeoxycholic acid 1250 mg
Sponsored by
About this trial
This is an interventional basic science trial for Type 2 Diabetes focused on measuring Type 2 diabetes, GLP-1, Bile acid, TGR-5
Eligibility 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
Sites / Locations
- Diabetes Research Division, Department of Internal Medicine, Gentofte Hospital, University of Copenhagen
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Colesevelam
Chenodeoxycholic acid
Colesevelam + chenodeoxycholic acid
Placebo
Arm Description
Outcomes
Primary Outcome Measures
Change in GLP-1
Secondary Outcome Measures
Change in insulin
Change in C-peptide
Change in glucagon
Change in glucagon-like-peptide 2 (GLP-2)
Change in glucose-dependent insulinotropic polypeptide (GIP)
Change in peptide YY (PYY)
Change in oxyntomodulin
Change in bile acids
Change in gastrin
Change in CCK
Change in appetite, satiety and prospective food consumption
Evaluated by Visual Analog Scale (VAS)
Change in gallbladder volume
Evaluated by ultrasound
Change in basal metabolic rate
Evaluated by indirect calorimetry
Change in bile acid composition
Evaluated by duodenal aspiration
Full Information
NCT ID
NCT01666223
First Posted
July 11, 2012
Last Updated
December 21, 2013
Sponsor
University Hospital, Gentofte, Copenhagen
1. Study Identification
Unique Protocol Identification Number
NCT01666223
Brief Title
Effect of Bile Acids on GLP-1 Secretion
Official Title
Effect of Bile Acids in the Gut on GLP-1 Secretion in Healthy Subjects and Patients With Type 2 Diabetes
Study Type
Interventional
2. Study Status
Record Verification Date
December 2013
Overall Recruitment Status
Completed
Study Start Date
November 2012 (undefined)
Primary Completion Date
June 2013 (Actual)
Study Completion Date
June 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University Hospital, Gentofte, Copenhagen
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 2 Diabetes, Obesity
Keywords
Type 2 diabetes, GLP-1, Bile acid, TGR-5
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
20 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Colesevelam
Arm Type
Experimental
Arm Title
Chenodeoxycholic acid
Arm Type
Experimental
Arm Title
Colesevelam + chenodeoxycholic acid
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Colesevelam
Intervention Description
Colesevelam 3750 mg dissolved in 100 ml saline, administered in a feeding tube at time = 0.
Intervention Type
Drug
Intervention Name(s)
Chenodeoxycholic Acid
Intervention Description
1.250 mg dissolved in 100 ml saline, administered in a feeding tube at time = 0.
Intervention Type
Other
Intervention Name(s)
saline
Intervention Description
100 ml saline
Intervention Type
Drug
Intervention Name(s)
Colesevelam 3750 mg + chenodeoxycholic acid 1250 mg
Intervention Description
Colesevelam and chenodeoxycholic acid dissolved in 100 ml saline, administered in a duodenal tube at time = 0.
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
Change in insulin
Time Frame
At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes
Title
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
Title
Change in glucagon
Time Frame
At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes
Title
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
Title
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
Title
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
Title
Change in oxyntomodulin
Time Frame
At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes
Title
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
Title
Change in gastrin
Time Frame
At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes
Title
Change in CCK
Time Frame
At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes
Title
Change in appetite, satiety and prospective food consumption
Description
Evaluated by Visual Analog Scale (VAS)
Time Frame
At baseline, and 30, 60, 90, 120 and 180 minutes
Title
Change in gallbladder volume
Description
Evaluated by ultrasound
Time Frame
-30, 0 (baseline), 30, 60, 120 og 180 minutes
Title
Change in basal metabolic rate
Description
Evaluated by indirect calorimetry
Time Frame
At -30, 60 og 150 minutes
Title
Change in bile acid composition
Description
Evaluated by duodenal aspiration
Time Frame
At -30, 0, 30, 60, 120 og 180 minutes
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Morten Hansen, MD
Organizational Affiliation
Diabetes Research Division, Department of Internal Medicine, Gentofte Hospital, University of Copenhagen
Official's Role
Principal Investigator
Facility Information:
Facility Name
Diabetes Research Division, Department of Internal Medicine, Gentofte Hospital, University of Copenhagen
City
Hellerup
State/Province
Copenhagen
Country
Denmark
12. IPD Sharing Statement
Citations:
PubMed Identifier
12419312
Citation
Maruyama T, Miyamoto Y, Nakamura T, Tamai Y, Okada H, Sugiyama E, Nakamura T, Itadani H, Tanaka K. Identification of membrane-type receptor for bile acids (M-BAR). Biochem Biophys Res Commun. 2002 Nov 15;298(5):714-9. doi: 10.1016/s0006-291x(02)02550-0.
Results Reference
background
PubMed Identifier
8406158
Citation
Adrian TE, Ballantyne GH, Longo WE, Bilchik AJ, Graham S, Basson MD, Tierney RP, Modlin IM. Deoxycholate is an important releaser of peptide YY and enteroglucagon from the human colon. Gut. 1993 Sep;34(9):1219-24. doi: 10.1136/gut.34.9.1219.
Results Reference
background
PubMed Identifier
15721318
Citation
Katsuma S, Hirasawa A, Tsujimoto G. Bile acids promote glucagon-like peptide-1 secretion through TGR5 in a murine enteroendocrine cell line STC-1. Biochem Biophys Res Commun. 2005 Apr 1;329(1):386-90. doi: 10.1016/j.bbrc.2005.01.139.
Results Reference
background
PubMed Identifier
21521075
Citation
Rafferty EP, Wylie AR, Hand KH, Elliott CE, Grieve DJ, Green BD. Investigating the effects of physiological bile acids on GLP-1 secretion and glucose tolerance in normal and GLP-1R(-/-) mice. Biol Chem. 2011 Apr;392(6):539-46. doi: 10.1515/BC.2011.050. Epub 2011 Apr 27.
Results Reference
background
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Effect of Bile Acids on GLP-1 Secretion
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