Clinical trial NCT03954873: Glucagon-like Peptide 2 - a Glucose Dependent Glucagonotropic Hormone?
Official title: Glucagon-like Peptide 2 - a Glucose Dependent Glucagonotropic Hormone?
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Glucose Metabolism Disorders
Endocrine or Metabolic Disease
Keywords: GLP-2
Glucagon
Lead sponsor: University Hospital, Gentofte, Copenhagen
Sponsor class: OTHER
First posted: 2019-05-17
Enrollment: 10
Sex: MALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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

Primary outcomes:
measure: Glucagon secretion
timeFrame: 110 minutes
Secondary outcomes:
measure: Plasma glucose
timeFrame: 110 minutes
measure: GLP-1
timeFrame: 110 minutes
measure: GLP-2
timeFrame: 110 minutes
measure: Insulin
timeFrame: 110 minutes
measure: GIP
timeFrame: 110 minutes
measure: OXM
timeFrame: 110 minutes
measure: Amino acids
timeFrame: 110 minutes
measure: CCK
timeFrame: 110 minutes
measure: Gastrin
timeFrame: 110 minutes
measure: FGF-19
timeFrame: 110 minutes
measure: FGF-21
timeFrame: 110 minutes
measure: Bile acids
timeFrame: 110 minutes
measure: Norepinephrine
timeFrame: 110 minutes
measure: GH
timeFrame: 110 minutes
measure: P1NP
timeFrame: 110 minutes
measure: CTX
timeFrame: 110 minutes
measure: Gallbladder ultrasound
timeFrame: 110 minutes
measure: Glucose infusion
timeFrame: 90 minutes
measure: Blood pressure
timeFrame: 110 minutes
measure: Heart rate
timeFrame: 110 minutes
measure: C-peptide
timeFrame: 110 minutes
Other outcomes:
Locations:
city: Hellerup
country: Denmark
facility: Center for Clinical Metabolic Research
state: Copenhagen
Study officials:
affiliation: Center for Clinical Metabolic Research
name: Filip Krag Knop, MD, PhD
role: STUDY_DIRECTOR
References: