Clinical trial NCT05391581: The Role of GIP and GLP-2 in Postprandial Splanchnic Blood Flow Distribution and Metabolism
Official title: The Role of the Intestinal Hormones Glucose-dependent Insulinotropic Polypeptide (GIP) and Glucagon-like Peptide 2 (GLP-2) in Postprandial Splanchnic Blood Flow Distribution and Metabolism in Humans
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Blood Flow
Keywords: Gut hormones
GIP
GLP-2
Physiology
Lead sponsor: University of Copenhagen
Sponsor class: OTHER
Collaborators: name: Rigshospitalet, Denmark
First posted: 2022-05-26
Enrollment: 10
Sex: MALE
Minimum age (years): 20
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Single blind, placebo controlled, randomized, crossover study
Primary purpose: BASIC_SCIENCE

Brief summary: This project will describe the mechanisms of action and the relative contributions of GIP and GLP-2 to changes in gastrointestinal blood flow induced by oral glucose, exogenous GIP and GLP-2 infusions, and endogenous GIP and GLP-2 with the use of two novel receptor antagonists GIP(3-30)NH2 and GLP-2(3-33) in healthy individuals.

Detailed description: Each participant will attend eight independent randomised experimental days in the MRI-scanner with intravenous infusion (hormone/placebo), subcutaneous injection (hormon/placebo) and oral ingestion (glucose/water). On experimental day A-C, an intravenous infusion of saline, GIP(3-30)NH2, or GLP-2(3-33), respectively, starts at time point -20 minutes. On experimental day D-F, the same infusions are combined with an oral glucose tolerance test (75 gram of glucose dissolved in 250 ml water ingested orally) at time point 0 minutes. On experimental days G-H, a subcutaneous injection of either GIP or GLP-2 at time point 0 minutes is performed (positive control) during saline infusion and oral water ingestion.

MRI measurements are repeatedly performed and blood samples are drawn to be analysed for endocrine responses from the intestines, pancreas, and bones.

Eligibility criteria: Inclusion Criteria:

* No first degree relatives with diabetes
* BMI 20-27 kg/m2

Exclusion Criteria:

* Not MRI-compatible implants
* Claustrophobia
* Diabetes
* Abnormal kidney or liver function
* Anemia
* Planned weight loss or change in diet
* Hypertension
* Other conditions that could be expected to affect the primary or secondary outcomes

Primary outcomes:
measure: Redistribution of splanchnic blood flow (functional MRI)
timeFrame: 90 minutes
Secondary outcomes:
measure: GIP levels
timeFrame: 90 minutes
measure: GLP-2 levels
timeFrame: 90 minutes
measure: GIP(3-30)NH2 levels
timeFrame: 90 minutes
measure: GLP-2(1-33) levels
timeFrame: 90 minutes
measure: CTX (bone resorption marker)
timeFrame: 90 minutes
measure: P1NP (bone formation marker)
timeFrame: 90 minutes
measure: Glucose
timeFrame: 90 minutes
measure: C-peptide
timeFrame: 90 minutes
measure: Insulin
timeFrame: 90 minutes
measure: Glucagon
timeFrame: 90 minutes
measure: Heart rate
timeFrame: 90 minutes
measure: Flow in coeliac trunk
timeFrame: 90 minutes
measure: Flow in hepatic artery
timeFrame: 90 minutes
measure: Flow in portal vein
timeFrame: 90 minutes
measure: Liver oxygen content
timeFrame: 90 minutes
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Rigshospitalet
Study officials:
References: