The Role of Endogenous GIP in Glycosis Metabolism During Fasting

GA-18: The Role of Endogenous GIP in Glycosis Metabolism During Fasting

This research project aims to investigate the role of endogenous GIP during fasting. With the infusion of a GIP receptor antagonist (GIP[3-30]NH2), is it possible to selectively remove the effect of endogenous GIP, and thus describe its effects by comparing it with what happens during a saline infusion.

Study Overview

• Status: Enrolling by invitation
• Conditions: Obesity
• Intervention / Treatment: Biological: GIP[3-30]NH2; Other: Saline

Detailed Description

This research project investigates the effects endogenous GIP has in the body of healthy, overweight people. Two trial days will be held. The participant will receive intravenous infusion of either GIP[3-30]NH2 (800 pmol/kg/min) or placebo (saline) in a randomized order. After 20 minutes, GIP[3-30]NH2 is expected to have maximum effect. On time of 180 minutes, an ad libitum meal is served, which is consumed during continued infusion. When the participant is comfortably full, the infusion is turned off and the trial day ends. During the day, the participant assesses and notes on standardized VAS schedules current appetite, satiety, nausea, fatigue, malaise and thirst. Blood pressure and heart rate are measured every 30 minutes throughout the trial day and blood samples are taken. In total, there will be drawn ten blood samples between intervals of 15 to 30 min. Three times along the way, the activity in the brown adipose tissue is measured with a thermal camera (temperature measurements over the skin on the chest) and the resting metabolic rate is determined with indirect calorimetry (inhaled and exhaled air is captured by breathing under a large plastic bell).

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Denmark
  • Hellerup, Denmark, 2900
    • Gentofte Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 18-70 years
• BMI > 30 kg/m2
• Body fat percentage > 25 % for men og > 35 % for women

Exclusion Criteria:

• Type 1 diabetes and/or type 2 diabetes diagnosis
• Other chronic condition
• Treatment with medications or supplements that cannot be paused for 12 hours
• > 14 units of alcohol weekly or drug abuse
• Circulating liver enzymes (alanine aminotransferase (ALAT) and/or aspartate aminotransferase (ASAT)) ≥ 2 × normal value
• Renal impairment (eGFR < 90 or creatinine level above the reference range)
• Uncontrolled high resting blood pressure (above 140/90 mmHg)
• Low blood percentage (hemoglobin < reference range (different for women and men))
• Special diet or planned weight change within the trial period
• Any disease/condition that investigators believe will interfere with study participation

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GIP[3-30]NH2 infusion; GIP[3-30]NH2 intravenous infusion (800 pmol/kg/min)	Biological: GIP[3-30]NH2; GIP[3-30]NH2 is the naturally occurring shorter (truncated) variant of GIP[1-42]. GIP[3-30]NH2 also stimulates the GIP receptor and therefore acts like a GIP receptorantagonist
Placebo Comparator: Saline infusion; Saline intravenous infusion (0,5 % human serum albumin)	Other: Saline; Sodium chlorid with 0,5% human serum albumin.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma glucagon concentrations	Measured in mmol/L. The primary endpoint is plasma glucagon concentrations during GIP[3-30]NH2 infusion compared to placebo.Area under the curve (AUC) for plasma glucagon (AUCglucagon) is quantified both as absolute and in baseline-subtracted values (bsAUCglucagon) and the effect of the GIP receptor antagonist will be calculated as a percentage reduction of bsAUC glucagon relative to bsAUC glucagon during the placebo infusion.	Four hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma levels of C-peptide	Measured in mmol/L	Four hours
Plasma levels of insulin	Measured in mmol/L	Four hours
Resting metabolic rate	Measured in resting energy expenditure (REE) and respiratory quotient (RQ)	15 minutes
Activity in brown adipose tissue	Measured by thermal camera	10 minutes
Appetite	Measured in kilogram food intake	30 minutes
Blood pressure	mmHg	Pre-intervention at time -30 and -20 min. During infusion at time 0 min, 30 min, 60 min, 90 min, 120 min, 160 min and 180 min.
Puls	Beats pr. minutes	Pre-intervention at time -30 and -20 minutes. During infusion at time 0 minutes, 30 minutes, 60 minutes, 90 minutes, 120 minutes, 160 minutes, and 180 minutes

Collaborators and Investigators

• Sponsor: Frederikke Koefoed-Hansen

Study record dates

Study Major Dates

• Study Start (Actual): May 4, 2023
• Primary Completion (Actual): December 12, 2023
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: July 30, 2023
• First Submitted That Met QC Criteria: April 11, 2024
• First Posted (Actual): April 16, 2024

Study Record Updates

• Last Update Posted (Actual): April 16, 2024
• Last Update Submitted That Met QC Criteria: April 11, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: H-22063621

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The results of this project or sub-elements of the project will be compiled into one or more manuscripts for publication in one or more international scientific high impact journals. All results, both inconclusive, negative and positive trial results, will be published as soon as possible. All trial participants will be informed in writing of the results after the end of the trial.
• IPD Sharing Time Frame: December 31st. 2025
• IPD Sharing Supporting Information Type: 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