Glucagon-like Peptide 2 - a Glucose Dependent Glucagonotropic Hormone?

Not Applicable

Completed

• Conditions: Glucose Metabolism Disorders; Endocrine or Metabolic Disease
• Interventions: Other: Saline; Other: Glucagon-like peptide 2; Other: Glucose; Other: Insulin

• Registration Number: NCT03954873
• Lead Sponsor: University Hospital, Gentofte, Copenhagen

Brief Summary

Infusion of glucagon-like peptide 2 (GLP-2) during euglycaemia, hypoglycaemia and hyperglycaemia and evaluation of the effect on glucagon secretion in healthy subjects.

Detailed Description

This is a cross-over, randomized, double-blinded study in which 10 participants will undergo 6 experimental days each. The participants will have their plasma glucose clamped at either euglycaemia (fasting level), hypoglycemia (2,5 mmol/l) or hyperglycemia (10 mmol/l) during infusion of GLP-2 or saline (placebo)

The six days will be as follows:

* Euglycaemia + Placebo

* Euglycaemia + GLP-2

* Hyperglycaemia + Placebo

* Hyperglycaemia + GLP-2

* Hypoglycaemia + Placebo

* Hypoglycaemia + GLP-2

The primary endpoint will be levels of plasma glucagon. Secondary endpoint will be levels of GLP-1, GLP-2, Insulin/C-peptide, OXM, Amino acids, CCK, Gastrin, norepinephrine, bile acids, FGF-19/FGF-21. Secondary endpoints will also include ultrasound scan of the gallbladder.

Study Timeline

• Study Start: 2019-01-31
• Study First Submitted: 2019-05-15
• Study First Submitted QC: 2019-05-15
• Study First Posted: 2019-05-17
• Primary Completion: 2020-06-01
• Study Completion: 2020-06-01
• Status Verified: 2020-11
• Last Update Submitted: 2020-11-03
• Last Update Posted: 2020-11-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 10

Inclusion Criteria

• Caucasian ethnicity
• Body mass index (BMI): 18.5-27 kg/m2
• Glycated haemoglobin (HbA1c) < 42 mmol/mol
• Normal haemoglobin (8.3-10.5 mmol/l)
• Informed and oral and written consent

Exclusion Criteria

• Prediabetes, type 1 diabetes or type 2 diabetes or first-degree relatives with type 1 or type 2 diabetes
• Nephropathy (eGFR < 60 and/or albuminuria)
• Known liver disease and/or alanine transaminase (ALAT) or aspartate transaminase (ASAT) > 2 × upper normal limit
• Bilirubin > 25 μmol/l
• Known intestinal disease or previous surgery of the intestines
• Active or recent malignant disease
• Treatment with medicine that cannot be paused for 12 hours
• Any condition considered incompatible with participation by the investigators

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Hypoglycaemia + Saline	Saline	Insulin + glucose
Hypoglycaemia + GLP-2	Glucose	Insulin + glucose + GLP-2
Hyperglycaemia + GLP-2	Glucagon-like peptide 2	Glucose + GLP-2
Euglycaemia + Placebo	Saline	-
Hypoglycaemia + GLP-2	Insulin	Insulin + glucose + GLP-2
Hyperglycaemia + GLP-2	Glucose	Glucose + GLP-2
Hyperglycaemia + Placebo	Glucose	Glucose + saline
Hypoglycaemia + Saline	Glucose	Insulin + glucose
Hyperglycaemia + Placebo	Saline	Glucose + saline
Hypoglycaemia + GLP-2	Glucagon-like peptide 2	Insulin + glucose + GLP-2
Hypoglycaemia + Saline	Insulin	Insulin + glucose
Euglycaemia + GLP-2	Glucagon-like peptide 2	GLP-2

Primary Outcome Measures

Name	Time	Method
Glucagon secretion	110 minutes	Assessed by difference in absolute plasma glucagon concentrations (measured in pmol/liter) and incremental (baseline-subtracted) area under curve (AUC) for plasma glucagon

Secondary Outcome Measures

Name	Time	Method
Bile acids	110 minutes	Measured in nmol/ml
FGF-21	110 minutes	Fibroblast Growth factor 21, Measured in ng/mL
Plasma glucose	110 minutes	Measured in mmol/liter
GLP-2	110 minutes	Glucagon-like peptide 2, Measured in pmol/liter
OXM	110 minutes	Oxytomodulin, Measured in pmol/liter
Amino acids	110 minutes	Measured in pmol/liter
Gastrin	110 minutes	Measured in pmol/liter
Insulin	110 minutes	Measured in pmol/liter
CCK	110 minutes	Cholecystokinin, Measured in pmol/liter
GIP	110 minutes	Glucose dependent insulinotropic hormone, Measured in pmol/liter
FGF-19	110 minutes	Fibroblast Growth factor 19, Measured in ng/mL
GH	110 minutes	Growth hormone, Measured in nmol/ml
Norepinephrine	110 minutes	Measured in pmol/liter
CTX	110 minutes	C-terminal telopeptide (Bonemarker), Measured in nmol/ml
Heart rate	110 minutes	Heart rate (beats/minutes) in respons to GLP-2
P1NP	110 minutes	Procollagen type I N-terminal propeptide (Bonemarker), Measured in nmol/ml
Gallbladder ultrasound	110 minutes	Measuring of gallbladder size in respons to GLP-2
Glucose infusion	90 minutes	Amount of glucose infusion (20% v/w) in milliliters needed to clamp at isoglycemic levels (hyperglycemia and hypoglycemia) in respons to GLP-2
Blood pressure	110 minutes	Systolic (mmHg) and diastolic (mmHg) blood pressure in respons to GLP-2
C-peptide	110 minutes	Measured in pmol/liter
GLP-1	110 minutes	Glucagon-like peptide 1, Measured in pmol/liter

Trial Locations

Locations (1)

Center for Clinical Metabolic Research; 🇩🇰 Hellerup, Copenhagen, Denmark