Effect of Glucagon-like Peptide 2 on Gallbladder Motility After a Meal in Young, Healthy Male Subjects

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03682172
• Other study ID #: H-17037571
• Status: Active, not recruiting
• Phase: Early Phase 1
• Start date: May 1, 2018
• Est. completion date: July 1, 2020

Study information

• Verified date: June 2020
• Source: Steno Diabetes Center Copenhagen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 15
• Est. completion date: July 1, 2020
• Est. primary completion date: August 30, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 35 Years

Eligibility

Inclusion Criteria:

• Caucasian ethnicity

• Male

• Age: 18-35 years

• BMI: 18,5-24,9

• Fasting plasma glucose = 6 mmol/l

• Glycated haemoglobin (HbA1c) = 42 mmol/mol

• Normal haemoglobin (8,3-10,5 mmol/l)

• Informed and written consent

Exclusion Criteria:

• First-degree relatives with type 1 or type 2 diabetes

• Nephropathy (se-creatinin > 130 µM and/or albuminuria)

• Liver disease (alanintransaminase (ALAT) or aspartattransaminase (ASAT) > 2 × upper normal limit)

• Active or recent malignant disease

• Treatment with medicine that cannot be paused for 1 week

• Any treatment or condition requiring acute or sub-acute medical or surgical intervention

• Any condition considered incompatible with participation by the investigators

Related Conditions & MeSH terms

• Effect of Glucagon-like Peptide 2 on Gallbladder Motility

Intervention

Drug:
• GLP-2 (1pmol/kg/min)
Four hour intravenous infusion with glucagon-like peptide 2 at a rate of 1pmol/kg/min
• GLP-2 (10pmol/kg/min)
Four hour intravenous infusion with glucagon-like peptide 2 at a rate of 10 pmol/kg/min
• Placebo
Four hour intravenous infusion with saline water

Locations

Country	Name	City	State
Denmark	Clinical Metabolic Physiology, Steno Diabetes Center Copenhagen	Hellerup	Region Hovedstaden

Sponsors (1)

Lead Sponsor	Collaborator
Steno Diabetes Center Copenhagen

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Gallbladder ejection fraction (EF%)	Incremental Area Under the Curve (iAUC) for gallbladder ejection fraction (EF%) at time 0-210 minutes.	0-210 minutes
Secondary	Glucagon	Incremental Area Under the Curve (iAUC) (-30;200min) of glucagon plasma concentration.	-30-200 minutes
Secondary	Gastric emptying	Gastric emptying will be determined by the by paracetamol curve following ingestion of the meal (mixed with 1500 mg paracetamol).	0-200 minutes
Secondary	Time to maximum gallbladder EF%	Time to reach maximum gallbladder ejection fraction.	0-210 minutes