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

NCT ID: NCT02445508

Last Updated: 2017-05-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-05-31
• Study Completion Date: 2016-07-31

Brief 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.

Conditions

Diabetes Mellitus, Type 2

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

Placebo+Placebo

Oral ingestion of sevelamer placebo powder combined with intravenous infusion of isotonic saline.

Group Type: PLACEBO_COMPARATOR

Sevelamer placebo

Intervention Type: DRUG

Isotonic saline

Intervention Type: DRUG

Placebo+Cholecystokinin

Oral ingestion of sevelamer placebo powder combined with intravenous infusion of cholecystokinin.

Group Type: ACTIVE_COMPARATOR

Cholecystokinin

Intervention Type: DRUG

Sevelamer placebo

Intervention Type: DRUG

Sevelamer+Placebo

Oral ingestion of sevelamer powder combined with intravenous infusion of isotonic saline.

Group Type: ACTIVE_COMPARATOR

Sevelamer

Intervention Type: DRUG

Isotonic saline

Intervention Type: DRUG

Sevelamer+Cholecystokinin

Oral ingestion of sevelamer powder combined with intravenous infusion of cholecystokinin.

Group Type: ACTIVE_COMPARATOR

Sevelamer

Intervention Type: DRUG

Cholecystokinin

Intervention Type: DRUG

Interventions

Sevelamer

Intervention Type: DRUG

Cholecystokinin

Intervention Type: DRUG

Sevelamer placebo

Intervention Type: DRUG

Isotonic saline

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: collaborator

University Hospital, Gentofte, Copenhagen

OTHER

Sponsor Role: lead

Responsible Party

Andreas Brønden

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Center for Diabetes Research

Hellerup, , Denmark

Countries

Denmark

Other Identifiers

NCT02445508

Identifier Type: -

Identifier Source: org_study_id