- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02497313
Effect of Metformin and Cholecystokinin-mediated Gallbladder Emptying on GLP-1 Secretion in Type 2 Diabetes
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. Metformin will be applied as a tool to reduce bile acid reuptake in the small intestine; thereby increasing bile acid concentration in the more distal parts of the gut where GLP-1-secreting L cell are abundant. Interestingly, metformin has been shown to reduce the active reabsorption of bile acids in the ileum and cause increased faecal elimination of bile acids. Clinical data has suggested that metformin causes an increase in the postprandial secretion of GLP-1 in humans including patients with type 2 diabetes. Intravenous infusion of cholecystokinin will be used to elicit gallbladder contraction and emptying. The aim is to examine how (and if) modification of bile acid reabsorption 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.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
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Hellerup, Denmark, 2900
- Center for Diabetes Research, Herlev-Gentofte Hospital
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: Placebo+Placebo
Oral ingestion of metformin placebo combined with intravenous infusion of isotonic saline.
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Active Comparator: Placebo+Cholecystokinin
Oral ingestion of metformin placebo combined with intravenous infusion of cholecystokinin.
|
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Active Comparator: Metformin+Placebo
Oral ingestion of metformin combined with intravenous infusion of isotonic saline.
|
|
Active Comparator: Metformin+Cholecystokinin
Oral ingestion of metformin combined with intravenous infusion of cholecystokinin.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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)
|
-30, -15, 0, 10, 20, 30, 45, 60, 90, 120, 180, 240 min on study days 1-4
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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)
|
-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
Time Frame: -30, -15, 0, 10, 20, 30, 45, 60, 90, 120, 180, 240 min on study days 1-4
|
Assessment of gastric emptying
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-30, -15, 0, 10, 20, 30, 45, 60, 90, 120, 180, 240 min on study days 1-4
|
Indirect calorimetry: Basal metabolic rate
Time Frame: -30 min to 240 min
|
Basal metabolic rate
|
-30 min to 240 min
|
Gallbladder volume as assessed by Ultrasound measurements
Time Frame: -30 min to 240 min
|
Gallbladder volume
|
-30 min to 240 min
|
Appetite as assessed by Visual analog scale score
Time Frame: -30 min to 240 min
|
Appetite
|
-30 min to 240 min
|
Collaborators and Investigators
Investigators
- Principal Investigator: Andreas Brønden, MD, PhD student
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- H-15007280
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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