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

Sponsor

University Hospital, Gentofte, Copenhagen (Other)

Overall Status

Completed

CT.gov ID

NCT02445508

Collaborator

Sanofi (Industry)

Enrollment

Location

Arms

Duration (Months)

1.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 2	Drug: Sevelamer Drug: Cholecystokinin Drug: Sevelamer placebo Drug: Isotonic saline	N/A

Study Design

Study Type:

Interventional

Actual Enrollment :

15 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Basic Science

Official Title:

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

Study Start Date :

May 1, 2015

Actual Primary Completion Date :

Jul 1, 2016

Actual Study Completion Date :

Jul 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo+Placebo Oral ingestion of sevelamer placebo powder combined with intravenous infusion of isotonic saline.	Drug: Sevelamer placebo Drug: Isotonic saline
Active Comparator: Placebo+Cholecystokinin Oral ingestion of sevelamer placebo powder combined with intravenous infusion of cholecystokinin.	Drug: Cholecystokinin Drug: Sevelamer placebo
Active Comparator: Sevelamer+Placebo Oral ingestion of sevelamer powder combined with intravenous infusion of isotonic saline.	Drug: Sevelamer Drug: Isotonic saline
Active Comparator: Sevelamer+Cholecystokinin Oral ingestion of sevelamer powder combined with intravenous infusion of cholecystokinin.	Drug: Sevelamer Drug: Cholecystokinin

Outcome Measures

Primary Outcome Measures

Glucagon-like peptide-1 (GLP-1): Incremental and total area under the Concentration-Time Curve [-30, -15, 0, 10, 20, 30, 45, 60, 90, 120, 180, 240 min on study days 1-4]
Incremental and total area under the Concentration-Time Curve (AUC 0-240 min)

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Center for Diabetes Research	Hellerup		Denmark	2900

Sponsors and Collaborators

University Hospital, Gentofte, Copenhagen
Sanofi

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Andreas Brønden, MD, University Hospital, Gentofte, Copenhagen

ClinicalTrials.gov Identifier:

NCT02445508

Other Study ID Numbers:

NCT02445508

First Posted:

May 15, 2015

Last Update Posted:

May 3, 2017

Last Verified:

May 1, 2017

Additional relevant MeSH terms:

Diabetes Mellitus, Type 2

Cholecystokinin

Sevelamer

Study Results

No Results Posted as of May 3, 2017