Clinical trial NCT06194955: The Effect of GIP, GLP-1 and GLP-2 in Individuals With Genetically Altered Receptor Function
Official title: The Effect of Glucose-dependent Insulinotropic Polypeptide (GIP), Glucagon-like Peptide-1 (GLP-1) and Glucagon-like Peptide-2 (GLP-2) in Individuals With Genetically Altered Receptor Function
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Incretin Effect
Keywords: Gut hormones
single nucleotide variants (SNVs)
GIP
GLP-1
GLP-2
Lead sponsor: University of Copenhagen
Sponsor class: OTHER
Collaborators: name: Gentofte Hospital, Denmark
First posted: 2024-01-08
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Single-blind, randomized, crossover study
Primary purpose: BASIC_SCIENCE

Brief summary: This project will characterize the physiological effect of the hormones, GIP-, GLP-1- and GLP-2 infusions in a group of individuals that are carriers of GIP-, GLP-1- and GLP-2 receptor gene variants, respectively.

Detailed description: Participants with mutations in their GLP-1- and GIP receptor will attend five randomized experimental days, A1, A2, B, C and D. On day A1 an oral glucose tolerance test (OGTT) will be performed, and on day A2, an intravenous isoglycaemic glucose infusion (IIGI) will be performed. On experimental day B and C, the study participants will receive GLP-1 and GIP hormones, respectively, under stable glucose infusions and on experimental day D, they will receive infusion of salt water (placebo) under stable glucose infusion.

Participants with mutations in their GLP-2 receptor will attend three randomized experimental days, E, F and G. A mixed meal test (MMT) will be performed on day E, an infusion with GLP-2 during fasting blood glucose levels will be performed on day F, and infusion with salt water (placebo) during fasting blood glucose levels will be performed on day G.

Additionally, a DXA scan and arginine test will be performed on all study participants.

Eligibility criteria: Inclusion Criteria:

* BMI 19-35 kg/m2

Exclusion Criteria:

* Treatment with medication or supplements that can not be discontinued for 12 hours
* \>10 objects of alcohol weekly or abuse of narcotics
* Liver disease (defined as ALAT and/or ASAT ≥ 2 x normal levels)
* Decreased kidney function (creatine levels over reference interval)
* Uncontrollable increased blood pressure (\> 140/90 mmHg)
* Low blood percentage (hemoglobin \< 8.3 mmol/l)
* Special diet or planned weight change during trial period
* Other conditions that could be expected to affect the primary or secondary outcomes

Primary outcomes:
measure: For GIP- and GLP-1 receptor variants: Insulinotropic effect (C-peptide)
timeFrame: 240 minutes
measure: For GLP-2 receptor variants: CTX (bone resorption marker)
timeFrame: 120 minutes
Secondary outcomes:
measure: GIP levels
timeFrame: 240 minutes
measure: GLP-1 levels
timeFrame: 240 minutes
measure: GLP-2 levels
timeFrame: 240 minutes
measure: CTX (bone resorption marker)
timeFrame: 240 minutes
measure: P1NP (bone formation marker)
timeFrame: 240 minutes
measure: Heart rate
timeFrame: 240 minutes
measure: Insulin
timeFrame: 240 minutes
measure: Glucagon
timeFrame: 240 minutes
Other outcomes:
Locations:
city: Hellerup
country: Denmark
facility: Center for Clinical Metabolic Research, Gentofte Hospital
Study officials:
References: