Effect of Glucagon-like Peptide 2 on Gallbladder Motility Clinical Trial
Official title:
Effect of Glucagon-like Peptide 2 on Postprandial Gallbladder Motility in Healthy Subjects
The study will investigate the effect of the incretin hormone glucagon-like peptide 2 (GLP-2)
on postprandial gallbladder motility in young, healthy, male subjects.
The study is double-blinded, randomized and placebo controlled. 15 subjects will be included.
On three separate study days (A, B, C) the subjects will receive an four hour intravenous
infusion with either saline (placebo), GLP-2 at a rate of 1 pmol/kg/min or GLP-2 at a rate of
10 pmol/kg/min 30 minutes after the infusion start the subject will receive a liquid meal
which will stimulate gallbladder contraction.
The gallbladder volume will be determined by frequent ultrasonic scans, and blood samples
will be drawn on fixed times through out the study day.
Study design The primary endpoint is the incremental Area Under the Curve (iAUC) of the
gallbladder Ejection Fraction % (EF) at time 0-210 minutes. Gallbladder volume will be
measured during a four hour intravenous GLP-2 infusion at two different concentrations (1
pmol/kg body weight/min and 10pmol/kg body weight/min), respectively, compared to placebo
after ingestion of a liquid meal in healthy, young, male subjects. The gallbladder volume
will be quantified by multiple ultrasonography scans at fixed times during the experimental
study days.
Gallbladder ejection fraction (EF%) will be calculated as following:
Gallbladder EF = (gallbladder volume, baseline - gallbladder volume, at a given time t) /
gallbladder volume, baseline * 100. The gallbladder volume is determined by bedside
ultrasonography.
15 healthy male subjects will be included according to the inclusion and exclusion criteria
listed below.
Inclusion criteria:
Sex: Male Ethnicity: Caucasian Age: 18-35 years BMI: 18.5-24.9 Fasting plasma glucose: 6
mmol/l or below Glycated haemoglobin (HbA1c): 42 mmol/mol or below Haemoglobin: 8.3-10.5
mmol/l
Exclusion criteria:
First-degree relatives with type 1 or type 2 diabetes Nephropathy (serum creatinin > 130
micromole/l) Liver disease Active or recent malignant disease
A subject will participate in three study days (day A, B and C) with a minimum of 48 hours
between each day. The three days will differ in regards to the intravenous infusion:
Study day A (placebo):
Subjects arrive at the laboratory after an overnight fast (10h). Two cannulas will then be
inserted in the cubital veins (one in each arm) for collection of blood samples and
administration of saline (placebo), respectively. The forearm from which blood samples are
drawn will be wrapped in a heating pad throughout the experiment. The participant must rest
30 minutes before start of the experimental procedures.
At time -30 min, saline infusion (placebo) will be started.
At time 0 min the participant will ingest a mixed liquid meal (200 ml, 1260 kJ) mixed with
paracetamol (1,500 mg) dissolved in 100 ml of water.
At time -60, -30, -15, 0, 10, 30, 50, 70, 90, 120, 150, 180 and 210 min gallbladder height,
width and length will be determined by ultrasound (LOGIQ E9, GE Healthcare, Waukesha, WI,
USA) for evaluation of gallbladder volume (calculated by the ellipsoid method).
Blood samples will be collected at time -45, -40, -35, -20, -5, 20, 40, 60, 80, 100, 140 and
200 min for the analysis of plasma/serum concentrations of glucose, GLP-1, GLP-2, GIP,
glucagon, OXM, PYY, ghrelin, gastrin, CCK, FGF-19, insulin, C-peptide, bile acids, free fatty
acids, paracetamol and triglycerides.
Experimental Day B (GLP-2 (1 pmol/kg/min)) As experimental Day A, but with infusion of GLP-2
(1 pmol/kg/min) instead of the saline infusion.
Experimental Day C (GLP-2 (10 pmol/kg/min)) As experimental Day A, but with infusion of GLP-2
(10 pmol/kg/min) instead of the saline infusion.
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