Interplay Between Interleukin-6 and Glucagon in the Regulation of Human Amino Acid and Protein Homeostasis (IGLU)

The goal of this proof-of-concept study is to learn if interleukin-6 changes the effect of glucagon in healthy volunteers. The main question it aims to answer is:

Does IL-6 influence how effectively glucagon lowers the concentration of amino acids in blood? Researchers will compare the infusion of normal saline and a blocker of the receptor for interleukin-6 to see if blocking interluekin-6 changes how effectively glucagon lowers the concentration of amino acids in blood.

Participants will be asked to

• receive either an infusion of normal saline or the interleukin-6 receptor blocker
• participate in a study visit three weeks later at which they will receive infusions of hormones and amino acids to mimic the concentrations of the hormones insulin and glucagon during fasting or fed conditions
• labelled glucose, glycerol and amino acids will also be infused continuously to track the fate of these molecules
• during the hormone infusions blood samples will be taken repeatedly

Study Overview

• Status: Completed
• Conditions: Healthy; Amino Acid Change; Glucagon Resistance
• Intervention / Treatment: Other: Placebo; Drug: Tocilizumab

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Basel, Switzerland, 4031
    • University Hospital Basel

Participation Criteria

Eligibility Criteria

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

Description

Inclusion criteria:

• Age 18 to 50 years
• BMI 18.5 - 25 kg/m2
• Stable body weight in the past 6 months before study initiation
• Women should be anovulatory on non-cyclic hormone replacement or hormonal contraception

Exclusion criteria:

• Previous medical history for any chronic condition in the last three months, active disease or abnormal physical examination as verified by a qualified physician
• Body weight unstable in the past 6 months
• Use of tobacco/nicotine
• Alcohol consumption >30g/day
• Participation in an investigational drug trial within the past two months
• Current intake of any drugs (prescribed, over the counter or recreational)
• Known allergy to tocilizumab
• Pregnant or lactating women,
• Inability or unwillingness to provide informed consent

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Infusion of 100 ml normal saline	Other: Placebo; Infusion of 100 ml normal saline
Active Comparator: IL-6R ab; Infusion of tocilizumab, 8mg/kg body weight or max. 800mg in 100 ml normal saline	Drug: Tocilizumab; Blockade of the interleukin-6 receptor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in maximum glucagon-induced reduction in total plasma amino acid concentrations	At visit 2 during high glucagon phase (80-120 minutes)

Secondary Outcome Measures

Outcome Measure	Time Frame
AUC of total amino acids	At visit 2 during high glucagon phase (80-120 minutes)
rate of phenylalanine oxidation	At visit 2 (15, 30, 45, 60, 80, 100, 120, 140, 160, 180, 200, 220, 240, 260, 280, 300 minutes)
urea concentrations	At visit 2 (15, 30, 45, 60, 80, 100, 120, 140, 160, 180, 200, 220, 240, 260, 280, 300 minutes)
rate of gluconeogenesis from amino acids	At visit 2 (15, 30, 45, 60, 80, 100, 120, 140, 160, 180, 200, 220, 240, 260, 280, 300 minutes)
fractional synthesis rate of plasma proteins	At visit 2 (60, 180, 300 minutes)
Amino acid uptake by PBMCs ex vivo	At visit 1 and visit 2 (-120 minutes)
Change in fractional synthesis rate of lipoproteins	At visit 2 (60, 180, 300 minutes)
Cytokine plasma concentrations (IL-6, IL-1RA, TNF-alpha, IL-8, IL-10, CRP)	At visit 2 (15, 30, 45, 60, 80, 100, 120, 140, 160, 180, 200, 220, 240, 260, 280, 300 minutes)
Plasma concentrations of insulin, c-peptide, glucagon, GH, IGF-1, cortisol, catecholamines, fT4, fT3, FGF21, follistatin, AGPTL4, ketones	At visit 2 (15, 30, 45, 60, 80, 100, 120, 140, 160, 180, 200, 220, 240, 260, 280, 300 minutes)
Energy expenditure kcal/24 hours	At visit 2 (40, 160, 280 minutes)
Respiratory exchange rate	At visit 2 (40, 160, 280 minutes)
Oxygen consumption (VO2 ml/minutes)	At visit 2 (40, 160, 280 minutes)
Carbondioxid production (VCO2 ml/minutes)	At visit 2 (40, 160, 280 minutes)
Body composition (lean body mass kg)	At visit 1 and 2 (-120 minutes)
Body composition (fat bodymass kg)	At visit 1 and 2 (-120 minutes)
Blood pressure systolic	At visit 2 (-120 minutes)
Blood pressure diastolic	At visit 2 (-120 minutes)
Heart rate	At visit 2 (-120minutes)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in protein profiles	Using untargeted and targeted proteomic platforms, the changes in protein profiles in the plasma will be measured	At visit 2 (60, 180, 300 minutes)
Changes in metabolite profiles	Using untargeted and targeted metabolomic platforms, the changes in metabolite profiles in the plasma serum will be measured	At visit 2 (60, 180, 300 minutes)

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland
• Investigators: Principal Investigator: Beckey Trinh, MD, PhD, University Hospital, Basel, Switzerland

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2025
• Primary Completion (Actual): September 18, 2025
• Study Completion (Actual): September 18, 2025

Study Registration Dates

• First Submitted: March 30, 2024
• First Submitted That Met QC Criteria: December 3, 2024
• First Posted (Actual): December 6, 2024

Study Record Updates

• Last Update Posted (Estimated): October 3, 2025
• Last Update Submitted That Met QC Criteria: September 29, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: interleukin-6; gluagon; pancreatic clamp
• Additional Relevant MeSH Terms: tocilizumab
• Other Study ID Numbers: IGLU

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No