The Role of Endogenous GIP in Glycosis Metabolism During Fasting

Early Phase 1

• Conditions: Obesity
• Interventions: Biological: GIP[3-30]NH2; Other: Saline

• Registration Number: NCT06368752
• Lead Sponsor: Frederikke Koefoed-Hansen

Brief Summary

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.

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 Timeline

• Study Start: 2023-05-04
• Study First Submitted: 2023-07-30
• Primary Completion: 2023-12-12
• Status Verified: 2024-04
• Study First Submitted QC: 2024-04-11
• Last Update Submitted: 2024-04-11
• Study First Posted: 2024-04-16
• Last Update Posted: 2024-04-16
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 12

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
GIP[3-30]NH2 infusion	GIP[3-30]NH2	GIP\[3-30\]NH2 intravenous infusion (800 pmol/kg/min)
Saline infusion	Saline	Saline intravenous infusion (0,5 % human serum albumin)

Primary Outcome Measures

Name	Time	Method
Plasma glucagon concentrations	Four hours	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.

Secondary Outcome Measures

Name	Time	Method
Plasma levels of insulin	Four hours	Measured in mmol/L
Activity in brown adipose tissue	10 minutes	Measured by thermal camera
Resting metabolic rate	15 minutes	Measured in resting energy expenditure (REE) and respiratory quotient (RQ)
Plasma levels of C-peptide	Four hours	Measured in mmol/L
Appetite	30 minutes	Measured in kilogram food intake
Blood pressure	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.	mmHg
Puls	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	Beats pr. minutes

Trial Locations

Locations (1)

Gentofte Hospital; 🇩🇰 Hellerup, Denmark