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

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 Overview

• Status: Unknown
• Conditions: Effect of Glucagon-like Peptide 2 on Gallbladder Motility
• Intervention / Treatment: Drug: GLP-2 (10pmol/kg/min); Drug: GLP-2 (1pmol/kg/min); Drug: Placebo

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Denmark
  • Region Hovedstaden
    • Hellerup, Region Hovedstaden, Denmark, 2900
      • Clinical Metabolic Physiology, Steno Diabetes Center Copenhagen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: GLP-2 (10pmol/kg/min); A single four hour intravenous infusion with glucagon-like peptide 2 at a rate of 10pmol/kg/min	Drug: GLP-2 (10pmol/kg/min); Four hour intravenous infusion with glucagon-like peptide 2 at a rate of 10 pmol/kg/min
EXPERIMENTAL: GLP-2 (1pmol/kg/min); A single four hour intravenous infusion with glucagon-like peptide 2 at a rate of 1pmol/kg/min	Drug: GLP-2 (1pmol/kg/min); Four hour intravenous infusion with glucagon-like peptide 2 at a rate of 1pmol/kg/min
EXPERIMENTAL: Placebo; A single four hour intravenous infusion with saline water (placebo)	Drug: Placebo; Four hour intravenous infusion with saline water

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gallbladder ejection fraction (EF%)	Incremental Area Under the Curve (iAUC) for gallbladder ejection fraction (EF%) at time 0-210 minutes.	0-210 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glucagon	Incremental Area Under the Curve (iAUC) (-30;200min) of glucagon plasma concentration.	-30-200 minutes
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
Time to maximum gallbladder EF%	Time to reach maximum gallbladder ejection fraction.	0-210 minutes

Collaborators and Investigators

• Sponsor: Steno Diabetes Center Copenhagen
• Investigators: Principal Investigator: Filip K Knop, MD, phd, Clinical Metabolic Physiology, Steno Diabetes Center Copenhagen

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 1, 2018
• Primary Completion (ACTUAL): August 30, 2018
• Study Completion (ANTICIPATED): July 1, 2020

Study Registration Dates

• First Submitted: July 16, 2018
• First Submitted That Met QC Criteria: September 21, 2018
• First Posted (ACTUAL): September 24, 2018

Study Record Updates

• Last Update Posted (ACTUAL): June 25, 2020
• Last Update Submitted That Met QC Criteria: June 24, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: Gallbladder Motility; Gallbladder Emptying; Glucagon-Like Peptide 2
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Gastrointestinal Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Incretins; Glucagon; Glucagon-Like Peptide 1
• Other Study ID Numbers: H-17037571

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No