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

Not Applicable

Recruiting

• Conditions: Healthy; Glucagon Resistance; Amino Acid Change
• Interventions: Other: Placebo; Drug: Tocilizumab

• Registration Number: NCT06721910
• Lead Sponsor: University Hospital, Basel, Switzerland

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-03-30
• Study First Submitted QC: 2024-12-03
• Study First Posted: 2024-12-06
• Status Verified: 2025-01
• Study Start: 2025-01-15
• Last Update Submitted: 2025-01-29
• Last Update Posted: 2025-02-03
• Primary Completion: 2025-10
• Study Completion: 2025-10

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 26

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Infusion of 100 ml normal saline
IL-6R ab	Tocilizumab	Infusion of tocilizumab, 8mg/kg body weight or max. 800mg in 100 ml normal saline

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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)

Trial Locations

Locations (1)

University Hospital Basel; 🇨🇭 Basel, Switzerland