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NCT Number: NCT02445508

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

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.

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Key information

Conditions

Diabetes Mellitus, Type 2 Diabetes Mellitus Endocrine System Diseases Glucose Metabolism Disorders Metabolic Diseases Nutritional and Metabolic Diseases

Age range

40 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Center for Diabetes Research

Hellerup, 2900, Denmark

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Sevelamer

Drug

Cholecystokinin

Drug

Sevelamer placebo

Drug

Isotonic saline

Drug

Primary outcomes

  1. Glucagon-like peptide-1 (GLP-1): Incremental and total area under the Concentration-Time Curve

    Time frame: -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 outcomes

  1. Responses of various other gut hormones: Incremental and total area under the Concentration-Time Curve

    Time frame: -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)

  2. Blood analysis of paracetamol as an assessment of gastric emptying

    Time frame: -30, -15, 0, 10, 20, 30, 45, 60, 90, 120, 180, 240 min on study days 1-4

    Assessment of gastric emptying

  3. Indirect calorimetry: Basal metabolic rate

    Time frame: -30 min to 240 min

    Basal metabolic rate

  4. Gallbladder volume as assessed by Ultrasound measurements

    Time frame: -30 min to 240 min

    Gallbladder volume

  5. Appetite as assessed by Visual analog scale score

    Time frame: -30 min to 240 min

    Appetite

Sponsors and collaborators

Lead sponsor

University Hospital, Gentofte, Copenhagen

Other

Collaborators

  • Sanofi

Registry information

Important dates

Study start
2015
Primary completion
2016
Study completion
2016
First posted
May 15, 2015
Registry last updated
May 3, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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