The Role of GIP and GLP-2 in Postprandial Splanchnic Blood Flow Distribution and Metabolism (GA-17)

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

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.

Study Overview

• Status: Completed
• Conditions: Blood Flow
• Intervention / Treatment: Other: Placebo; Other: GIPR antagonist / study tool; Other: GLP-2R antagonist / study tool

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.

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

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark, 2200
    • Rigshospitalet

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: SAL-WAT; Saline infusion, saline injection, water ingestion	Other: Placebo; Saline
Active Comparator: SAL-GLU; Saline infusion, saline injection, glucose ingestion	Other: Placebo; Saline
Active Comparator: SAL-GIP; Saline infusion, GIP injection, water ingestion	Other: Placebo; Saline
Active Comparator: SAL-GLP-2; Saline infusion, GLP-2 injection, water ingestion	Other: Placebo; Saline
Experimental: GIA-WAT; GIPR antagonist infusion, saline injection, water ingestion	Other: Placebo; Saline; Other: GIPR antagonist / study tool; Selective antagonist of the GIPR, GIP(3-30)NH2
Experimental: GIA-GLU; GIPR antagonist infusion, saline injection, glucose ingestion	Other: GIPR antagonist / study tool; Selective antagonist of the GIPR, GIP(3-30)NH2
Experimental: GLA-WAT; GLP-2R antagonist infusion, saline injection, water ingestion	Other: Placebo; Saline; Other: GLP-2R antagonist / study tool; Selective antagonist of the GLP-2R, GLP-2(3-33)
Experimental: GLA-GLU; GLP-2R antagonist infusion, saline injection, glucose ingestion	Other: GLP-2R antagonist / study tool; Selective antagonist of the GLP-2R, GLP-2(3-33)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Redistribution of splanchnic blood flow (functional MRI)	Flow in mesenteric superior artery	90 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
GIP levels	Blood sample (pmol/L)	90 minutes
GLP-2 levels	Blood sample (pmol/L)	90 minutes
GIP(3-30)NH2 levels	Blood sample (nmol/L)	90 minutes
GLP-2(1-33) levels	Blood sample (nmol/L)	90 minutes
CTX (bone resorption marker)	Blood sample	90 minutes
P1NP (bone formation marker)	Blood sample	90 minutes
Glucose	Blood sample (mmol/L)	90 minutes
C-peptide	Blood sample (pmol/L)	90 minutes
Insulin	Blood sample (pmol/L)	90 minutes
Glucagon	Blood sample (pmol/L)	90 minutes
Heart rate	Beats/minute	90 minutes
Flow in coeliac trunk	Functional MRI estimated blood flow	90 minutes
Flow in hepatic artery	Functional MRI estimated blood flow	90 minutes
Flow in portal vein	Functional MRI estimated blood flow	90 minutes
Liver oxygen content	Functional MRI estimated oxygenation	90 minutes

Collaborators and Investigators

• Sponsor: University of Copenhagen
• Collaborators: Rigshospitalet, Denmark

Study record dates

Study Major Dates

• Study Start (Actual): January 13, 2022
• Primary Completion (Actual): February 7, 2023
• Study Completion (Actual): February 7, 2023

Study Registration Dates

• First Submitted: May 6, 2022
• First Submitted That Met QC Criteria: May 20, 2022
• First Posted (Actual): May 26, 2022

Study Record Updates

• Last Update Posted (Actual): December 26, 2023
• Last Update Submitted That Met QC Criteria: December 22, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: GIP; Physiology; Gut hormones; GLP-2
• Other Study ID Numbers: GA-17

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Will share upon requests
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ANALYTIC_CODE; CSR

Drug and device information, study documents

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