Skip to main content
OpenTrials
Completed

NCT Number: NCT03739268

GLP-1-mediated Gluco-metabolic Effects of Bile Acid Sequestration

The objective of this study is to investigate the potential GLP-1-mediated contribution to the well-established glucose-lowering effect of sevelamer-induced bile acid sequestration . Exendin9-39 has been demonstrated to act as a potent and specific GLP-1 receptor antagonist with no partial agonistic potential and is considered a useful tool in the assessment of GLP-1 physiology. The aim is to evaluate any contribution of sevelamer-induced GLP-1 secretion to the reduced plasma glucose concentrations observed after treatment with sevelamer. A randomised placebo-controlled cross-over study involving two 17-day treatment periods with sevelamer and placebo, respectively, in metformin-treated patients with type 2 diabetes, will be conducted. The impact of bile acid sequestration on GLP-1 secretion and effect will be examined during two randomised experimental days after 15 and 17 days of treatment with sevelamer (1,600 mg three times a day) and placebo, respectively. During each of these two experimental days, a meal test with concomitant exendin9-39 infusion or placebo will be performed (for evaluation of any GLP-1-mediated effects). Postprandial plasma glucose excursion is the primary endpoint, and secondary endpoints include postprandial plasma/serum excursions of insulin, C-peptide, GLP-1, glucagon, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-2 (GLP-2), peptide YY (PYY), oxyntomodulin, ghrelin, fibroblast growth factor (FGF)-19, FGF-21, C4 (an intermediate in the de novo synthesis of bile acids), cholecystokinin (CCK), bile acids and plasma lipids. Furthermore, gastric emptying, gallbladder emptying, liver fat content, appetite and ad libitum food intake will be examined.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Type 2 Diabetes Mellitus Diabetes Mellitus Diabetes Mellitus, Type 2 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

Steno Diabetes Center Copenhagen, Gentofte Hospital

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 glucose-lowering drug
  • Caucasian ethnicity
  • Normal haemoglobin
  • Age above 40 years and below 75 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- or hyperthyroidism
  • Hypo- or hypercalcaemia
  • Hypo- or 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

Sevelamer powder dissolved in water 1,600 mg three times a day for 17 days

Other names: Renvela

Placebo

Drug

placebo powder dissolved in water 1,600 mg three times a day for 17 days

Primary outcomes

  1. plasma glucose

    Time frame: -30 minutes to 240 minutes with ingestion of a meal at 0 minutes

    Postprandial plasma glucose (PG) excursion (AUC240 min)

Secondary outcomes

  1. Postprandial responses of glucagon-like peptide-1 (GLP-1)

    Time frame: -30 minutes to 240 minutes with ingestion of a meal at 0 minutes

    Meal response of GLP-1

  2. Postprandial responses of glucose-dependent insulinotropic polypeptide (GIP)

    Time frame: -30 minutes to 240 minutes with ingestion of a meal at 0 minutes

    Meal response of glucose-dependent insulinotropic polypeptide (GIP)

  3. Postprandial responses of glucagon-like peptide-2 (GLP-2)

    Time frame: -30 minutes to 240 minutes with ingestion of a meal at 0 minutes

    Meal response of glucagon-like peptide-2 (GLP-2)

  4. Postprandial responses of Glucagon

    Time frame: -30 minutes to 240 minutes with ingestion of a meal at 0 minutes

    Meal response of Glucagon

  5. Postprandial responses of peptide YY (PYY)

    Time frame: -30 minutes to 240 minutes with ingestion of a meal at 0 minutes

    Meal response of peptide YY (PYY)

  6. Postprandial responses of Insulin and c-peptide

    Time frame: -30 minutes to 240 minutes with ingestion of a meal at 0 minutes

    Meal response of Insulin and c-peptide as a insulin/c-peptide ratio

  7. Postprandial responses of Ghrelin

    Time frame: -30 minutes to 240 minutes with ingestion of a meal at 0 minutes

    Meal response of Ghrelin

  8. Postprandial responses of fibroblast growth factor (FGF)-19

    Time frame: -30 minutes to 240 minutes with ingestion of a meal at 0 minutes

    Meal response of fibroblast growth factor (FGF)-19

  9. Postprandial responses of fibroblast growth factor (FGF)-21

    Time frame: -30 minutes to 240 minutes with ingestion of a meal at 0 minutes

    Meal response of fibroblast growth factor (FGF)-21

  10. Postprandial responses of Bile acids

    Time frame: -30 minutes to 240 minutes with ingestion of a meal at 0 minutes

    Meal response of Bile acids

  11. Postprandial responses of cholecystokinin (CCK)

    Time frame: -30 minutes to 240 minutes with ingestion of a meal at 0 minutes

    Meal response of cholecystokinin (CCK)

  12. Postprandial responses of plasma lipids

    Time frame: -30 minutes to 240 minutes with ingestion of a meal at 0 minutes

    Meal response of plasma lipids

  13. Postprandial responses of Amino acids

    Time frame: -30 minutes to 240 minutes with ingestion of a meal at 0 minutes

    Meal response of Amino acids

  14. Gastric emptying

    Time frame: -30 minutes to 240 minutes with ingestion of a meal and paracetamol at 0 minutes

    Gastric emptying measured by paracetamol absorption test. Paracetamol is ingested along with meal, the appearance in blood will be calculated as a measure of gastric emptying.

  15. Rate of gall bladder emptying

    Time frame: -30 minutes to 240 minutes with ingestion of a meal at 0 minutes

    Gall bladder volumen measured by ultrasound over time after a meal (see time frame below). The rate of gall bladder emptying will be calculated

  16. Liver stiffness and fat

    Time frame: At initiation and after 15 days of treatment with sevelamer/placebo

    Liver stiffness and fat content measured by fibroscan

  17. Appetite measured by visual analog scale

    Time frame: -30 minutes to 240 minutes with ingestion of a meal at 0 minutes

    We assessed appetite parameters (hunger, satiety, fullness, prospective food consumption) and well-being, nausea, and thirst by visual analogue scales. Overall appetite score (OAS) will be calculated as (satiety + fullness + (100 - hunger) + (100 - prospective food consumption)

Sponsors and collaborators

Lead sponsor

Steno Diabetes Center Copenhagen

Other

Collaborators

  • Sanofi

Registry information

Acronym: SeveX

Important dates

Study start
2018
Primary completion
2020
Study completion
2021
First posted
Nov 13, 2018
Registry last updated
Oct 13, 2021

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.

Related clinical trials

Published trials that share one or more normalized conditions with this study.