The Effect of GIP, GLP-1 and GLP-2 in Individuals With Genetically Altered Receptor Function (H-21044858)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Incretin Effect
• Intervention / Treatment: Other: Placebo; Drug: GIP(1-42); Drug: GLP-1; Drug: GLP-2

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.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Lærke S Gasbjerg, MD, PhD; Phone Number: +45 35322626; Email: lsg@sund.ku.dk
• Study Contact Backup: Name: Sheyma Kizilkaya, MSc; Phone Number: +45 40502056; Email: sheyma@sund.ku.dk

Study Locations

• Denmark
  • Hellerup, Denmark, 2900
    • Recruiting
    • Center for Clinical Metabolic Research, Gentofte Hospital
    • Contact: Lærke S Gasbjerg; Email: lsg@sund.ku.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: GIPR variant carriers; Inidividuals with GIPR variants: Determination of the incretin effect, and the insulinotropic actions of GIP and GLP-1 infusions during hyperglycemic clamp.	Other: Placebo; Saline; Drug: GIP(1-42); Infusion; Drug: GLP-1; Infusion
Placebo Comparator: GIPR variant carrier controls; Healthy matched individuals: Determination of incretin effect, and the insulinotropic actions of GIP and GLP-1 infusions during hyperglycemic clamp.	Other: Placebo; Saline; Drug: GIP(1-42); Infusion; Drug: GLP-1; Infusion
Active Comparator: GLP-1R variant carrier; Individuals with GLP-1R variants: Determination of incretin effect, and the insulinotropic actions of GIP and GLP-1 infusions during hyperglycemic clamp	Other: Placebo; Saline; Drug: GIP(1-42); Infusion; Drug: GLP-1; Infusion
Placebo Comparator: GLP-1R variant carrier controls; Healthy matched individuals: Determination of incretin effect, and the insulinotropic actions of to GIP and GLP-1 infusions during hyperglycemic clamp.	Other: Placebo; Saline; Drug: GIP(1-42); Infusion; Drug: GLP-1; Infusion
Active Comparator: GLP-2R variant carrier; Individuals with GLP-2R variants: Determination of bone resorption marker levels (CTX) and response to GLP-2 infusions during fasting blood glucose levels	Other: Placebo; Saline; Drug: GLP-2; Infusion
Placebo Comparator: GLP-2R variant carrier control; Healthy matched individuals: Determination of bone resorption marker levels (CTX) and response to GLP-2 infusions during fasting blood glucose levels	Other: Placebo; Saline; Drug: GLP-2; Infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
For GIP- and GLP-1 receptor variants: Insulinotropic effect (C-peptide)	Blood sample	240 minutes
For GLP-2 receptor variants: CTX (bone resorption marker)	Blood sample	120 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
GIP levels	Blood sample	240 minutes
GLP-1 levels	Blood sample	240 minutes
GLP-2 levels	Blood sample	240 minutes
CTX (bone resorption marker)	Blood sample	240 minutes
P1NP (bone formation marker)	Blood Sample	240 minutes
Heart rate	Beats/minute	240 minutes
Insulin	Blood sample	240 minutes
Glucagon	Blood sample	240 minutes

Collaborators and Investigators

• Sponsor: University of Copenhagen
• Collaborators: Gentofte Hospital, Denmark

Study record dates

Study Major Dates

• Study Start (Actual): January 4, 2023
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: December 22, 2023
• First Submitted That Met QC Criteria: December 22, 2023
• First Posted (Actual): January 8, 2024

Study Record Updates

• Last Update Posted (Actual): May 7, 2024
• Last Update Submitted That Met QC Criteria: May 6, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: GLP-1; GIP; Gut hormones; GLP-2; single nucleotide variants (SNVs)
• Other Study ID Numbers: H-21044858

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

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