Effect of Bile Acids on GLP-1 Secretion

Obesity Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01666223
• Other study ID #: H-1-2012-049
• Status: Completed
• Phase: N/A
• First received: July 11, 2012
• Last updated: December 21, 2013
• Start date: November 2012
• Est. completion date: June 2013

Study information

• Verified date: December 2013
• Source: University Hospital, Gentofte, Copenhagen
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: The Danish National Committee on Biomedical Research Ethics
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: June 2013
• Est. primary completion date: June 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Obesity
• Type 2 Diabetes

Intervention

Drug:
• Colesevelam
Colesevelam 3750 mg dissolved in 100 ml saline, administered in a feeding tube at time = 0.
• Chenodeoxycholic Acid
1.250 mg dissolved in 100 ml saline, administered in a feeding tube at time = 0.

Other:
• saline
100 ml saline

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.

Locations

Country	Name	City	State
Denmark	Diabetes Research Division, Department of Internal Medicine, Gentofte Hospital, University of Copenhagen	Hellerup	Copenhagen

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Gentofte, Copenhagen

Country where clinical trial is conducted

Denmark, 

References & Publications (4)

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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in GLP-1		At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes	No
Secondary	Change in insulin		At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes	No
Secondary	Change in C-peptide		At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes	No
Secondary	Change in glucagon		At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes	No
Secondary	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	No
Secondary	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	No
Secondary	Change in peptide YY (PYY)		At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes	No
Secondary	Change in oxyntomodulin		At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes	No
Secondary	Change in bile acids		At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes	No
Secondary	Change in gastrin		At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes	No
Secondary	Change in CCK		At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes	No
Secondary	Change in appetite, satiety and prospective food consumption	Evaluated by Visual Analog Scale (VAS)	At baseline, and 30, 60, 90, 120 and 180 minutes	No
Secondary	Change in gallbladder volume	Evaluated by ultrasound	-30, 0 (baseline), 30, 60, 120 og 180 minutes	No
Secondary	Change in basal metabolic rate	Evaluated by indirect calorimetry	At -30, 60 og 150 minutes	No
Secondary	Change in bile acid composition	Evaluated by duodenal aspiration	At -30, 0, 30, 60, 120 og 180 minutes	No