Effect of Bile Acid Secretion and Sequestration on GLP-1 Secretion

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

Effect of Bile Acid Secretion and Sequestration on GLP-1 Secretion

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02445508
• Other study ID #: NCT02445508
• Status: Completed
• Phase: N/A
• First received: May 8, 2015
• Last updated: May 2, 2017
• Start date: May 2015
• Est. completion date: July 2016

Study information

• Verified date: May 2017
• Source: University Hospital, Gentofte, Copenhagen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Accumulating evidence suggests that bile acids in our intestines may constitute essential components in the complex mechanisms regulating gut hormone secretion and glucose homeostasis. Thus, it is likely that modification of the enterohepatic circulation of bile acids can lead to changes in gut hormone secretion and consequently affect glucose homeostasis.

The current study is a human interventional randomized controlled cross-over study including four study days for each participant. As a tool to sequester bile acids we will use sevelamer, a phosphate binding resin used in the treatment of hyperphosphataemia in adult patients with chronic kidney disease. Surprisingly, sevelamer has been shown to improve glycaemic control in patients with chronic kidney disease and type 2 diabetes. Intravenous infusion of cholecystokinin will be used to elicit gallbladder contraction and emptying. The aim is to examine how (and if) bile acid sequestration can influence postprandial glucagon-like peptide-1 (GLP-1) secretion and glucose homeostasis in patients with type 2 diabetes.

The investigators hypothesize that higher luminal concentrations of bile acids in the distal gut will elicit changes in gut hormone secretion. The current study will help to clarify this hypothesis and improve our general understanding of the association between bile acid circulation and signalling, gut hormone secretion and glucose metabolism.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: July 2016
• Est. primary completion date: July 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 75 Years

Eligibility

Inclusion Criteria:

• Type 2 diabetes for at least 3 months (diagnosed according to the criteria of the World Health Organization (WHO))

• Men and postmenopausal women

• Metformin applied as the only anti-diabetic drug

• Caucasian ethnicity

• Normal haemoglobin

• Age above 40 years and below 70 years

• BMI >23 kg/m2 and <35 kg/m2

• Informed and written consent

Exclusion Criteria:

• Liver disease (alanine aminotransferase (ALAT) and/or serum aspartate aminotransferase (ASAT) >2 times normal values) or history of hepatobiliary disorder

• Gastrointestinal disease, previous intestinal resection, cholecystectomy or any major intra-abdominal surgery

• Nephropathy (serum creatinine >150 µM and/or albuminuria)

• Hypo- and hyperthyroidism

• Hypo- and hypercalcaemia

• Hypo- and hyperphosphataemia

• Active or recent malignant disease

• Treatment with medicine that cannot be paused for 12 hours

• Treatment with oral anticoagulants

• Any treatment or condition requiring acute or sub-acute medical or surgical intervention

• Any condition considered incompatible with participation by the investigators

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• Sevelamer

• Cholecystokinin

• Sevelamer placebo

• Isotonic saline

Locations

Country	Name	City	State
Denmark	Center for Diabetes Research	Hellerup

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Gentofte, Copenhagen	Sanofi

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Glucagon-like peptide-1 (GLP-1): Incremental and total area under the Concentration-Time Curve	Incremental and total area under the Concentration-Time Curve (AUC 0-240 min)	-30, -15, 0, 10, 20, 30, 45, 60, 90, 120, 180, 240 min on study days 1-4
Secondary	Responses of various other gut hormones: Incremental and total area under the Concentration-Time Curve	Incremental and total area under the Concentration-Time Curve (AUC 0-240 min)	-30, -15, 0, 10, 20, 30, 45, 60, 90, 120, 180, 240 min on study days 1-4
Secondary	Blood analysis of paracetamol as an assessment of gastric emptying	Assessment of gastric emptying	-30, -15, 0, 10, 20, 30, 45, 60, 90, 120, 180, 240 min on study days 1-4
Secondary	Indirect calorimetry: Basal metabolic rate	Basal metabolic rate	-30 min to 240 min
Secondary	Gallbladder volume as assessed by Ultrasound measurements	Gallbladder volume	-30 min to 240 min
Secondary	Appetite as assessed by Visual analog scale score	Appetite	-30 min to 240 min