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

NCT02445508 | Completed

• 1 other identifier: NCT02445508
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• 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

• 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

• Indirect calorimetry: Basal metabolic rate

  -30 min to 240 min

• Gallbladder volume as assessed by Ultrasound measurements

  -30 min to 240 min

• Appetite as assessed by Visual analog scale score

  -30 min to 240 min

Study Arms (4)

Placebo+Placebo

PLACEBO COMPARATOR

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

Drug: Sevelamer placebo; Drug: Isotonic saline

Placebo+Cholecystokinin

ACTIVE COMPARATOR

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

Drug: Cholecystokinin; Drug: Sevelamer placebo

Sevelamer+Placebo

ACTIVE COMPARATOR

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

Drug: Sevelamer; Drug: Isotonic saline

Sevelamer+Cholecystokinin

ACTIVE COMPARATOR

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

Drug: Sevelamer; Drug: Cholecystokinin

Interventions

Sevelamer DRUG

Sevelamer+Cholecystokinin; Sevelamer+Placebo

Cholecystokinin DRUG

Placebo+Cholecystokinin; Sevelamer+Cholecystokinin

Sevelamer placebo DRUG

Placebo+Cholecystokinin; Placebo+Placebo

Isotonic saline DRUG

Placebo+Placebo; Sevelamer+Placebo

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Gentofte, Copenhagen: lead
• Sanofi: collaborator

Study Sites (1)

Center for Diabetes Research

Hellerup, 2900, Denmark

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Sevelamer; Cholecystokinin; Sodium Chloride

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Polyamines; Amines; Organic Chemicals; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: May 8, 2015
• First Posted: May 15, 2015
• Study Start: May 1, 2015
• Primary Completion: July 1, 2016
• Study Completion: July 1, 2016
• Last Updated: May 3, 2017

Record last verified: 2017-05

Locations

DK (1)