Glucagon-like Peptide 2 - a Glucose Dependent Glucagonotropic Hormone? (GLANCE)

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

Study Overview

• Status: Completed
• Conditions: Glucose Metabolism Disorders; Endocrine or Metabolic Disease
• Intervention / Treatment: Other: Saline; Other: Glucagon-like peptide 2; Other: Glucose; Other: Insulin

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 Type: Interventional
• Enrollment (Actual): 10
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen
    • Hellerup, Copenhagen, Denmark, 2900
      • Center for Clinical Metabolic Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Hyperglycaemia + GLP-2; Glucose + GLP-2	Other: Glucagon-like peptide 2; Human glucagon-like peptide 2; Other: Glucose; 20% (w/v) glucose infusion for regulating plasma glucose
ACTIVE_COMPARATOR: Hyperglycaemia + Placebo; Glucose + saline	Other: Saline; Placebo; Other: Glucose; 20% (w/v) glucose infusion for regulating plasma glucose
EXPERIMENTAL: Hypoglycaemia + GLP-2; Insulin + glucose + GLP-2	Other: Glucagon-like peptide 2; Human glucagon-like peptide 2; Other: Glucose; 20% (w/v) glucose infusion for regulating plasma glucose; Other: Insulin; Actrapid (insulin) for lowering plasma glucose
ACTIVE_COMPARATOR: Hypoglycaemia + Saline; Insulin + glucose	Other: Saline; Placebo; Other: Glucose; 20% (w/v) glucose infusion for regulating plasma glucose; Other: Insulin; Actrapid (insulin) for lowering plasma glucose
EXPERIMENTAL: Euglycaemia + GLP-2; GLP-2	Other: Glucagon-like peptide 2; Human glucagon-like peptide 2
ACTIVE_COMPARATOR: Euglycaemia + Placebo	Other: Saline; Placebo

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: University Hospital, Gentofte, Copenhagen
• Investigators: Study Director: Filip Krag Knop, MD, PhD, Center for Clinical Metabolic Research

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 31, 2019
• Primary Completion (ACTUAL): June 1, 2020
• Study Completion (ACTUAL): June 1, 2020

Study Registration Dates

• First Submitted: May 15, 2019
• First Submitted That Met QC Criteria: May 15, 2019
• First Posted (ACTUAL): May 17, 2019

Study Record Updates

• Last Update Posted (ACTUAL): November 4, 2020
• Last Update Submitted That Met QC Criteria: November 3, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: Glucagon; GLP-2
• Additional Relevant MeSH Terms: Metabolic Diseases; Glucose Metabolism Disorders; Physiological Effects of Drugs; Gastrointestinal Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Incretins; Glucagon; Glucagon-Like Peptide 1
• Other Study ID Numbers: H-18046965

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: IPD will not be shared with other researchers unless data management agreements are signed.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No