Clinical trial NCT06721910: Interplay Between Interleukin-6 and Glucagon in the Regulation of Human Amino Acid and Protein Homeostasis
Official title: Interplay Between Interleukin-6 and Glucagon in the Regulation of Human Amino Acid and Protein Homeostasis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Healthy
Glucagon Resistance
Amino Acid Change
Keywords: interleukin-6
gluagon
pancreatic clamp
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
First posted: 2024-12-06
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, double-blind, parallel
Primary purpose: BASIC_SCIENCE

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


Eligibility criteria: 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

Primary outcomes:
measure: Change in maximum glucagon-induced reduction in total plasma amino acid concentrations
timeFrame: At visit 2 during high glucagon phase (80-120 minutes)
Secondary outcomes:
measure: AUC of total amino acids
timeFrame: At visit 2 during high glucagon phase (80-120 minutes)
measure: rate of phenylalanine oxidation
timeFrame: At visit 2 (15, 30, 45, 60, 80, 100, 120, 140, 160, 180, 200, 220, 240, 260, 280, 300 minutes)
measure: urea concentrations
timeFrame: At visit 2 (15, 30, 45, 60, 80, 100, 120, 140, 160, 180, 200, 220, 240, 260, 280, 300 minutes)
measure: rate of gluconeogenesis from amino acids
timeFrame: At visit 2 (15, 30, 45, 60, 80, 100, 120, 140, 160, 180, 200, 220, 240, 260, 280, 300 minutes)
measure: fractional synthesis rate of plasma proteins
timeFrame: At visit 2 (60, 180, 300 minutes)
measure: Amino acid uptake by PBMCs ex vivo
timeFrame: At visit 1 and visit 2 (-120 minutes)
measure: Change in fractional synthesis rate of lipoproteins
timeFrame: At visit 2 (60, 180, 300 minutes)
measure: Cytokine plasma concentrations (IL-6, IL-1RA, TNF-alpha, IL-8, IL-10, CRP)
timeFrame: At visit 2 (15, 30, 45, 60, 80, 100, 120, 140, 160, 180, 200, 220, 240, 260, 280, 300 minutes)
measure: Plasma concentrations of insulin, c-peptide, glucagon, GH, IGF-1, cortisol, catecholamines, fT4, fT3, FGF21, follistatin, AGPTL4, ketones
timeFrame: At visit 2 (15, 30, 45, 60, 80, 100, 120, 140, 160, 180, 200, 220, 240, 260, 280, 300 minutes)
measure: Energy expenditure kcal/24 hours
timeFrame: At visit 2 (40, 160, 280 minutes)
measure: Respiratory exchange rate
timeFrame: At visit 2 (40, 160, 280 minutes)
measure: Oxygen consumption (VO2 ml/minutes)
timeFrame: At visit 2 (40, 160, 280 minutes)
measure: Carbondioxid production (VCO2 ml/minutes)
timeFrame: At visit 2 (40, 160, 280 minutes)
measure: Body composition (lean body mass kg)
timeFrame: At visit 1 and 2 (-120 minutes)
measure: Body composition (fat bodymass kg)
timeFrame: At visit 1 and 2 (-120 minutes)
measure: Blood pressure systolic
timeFrame: At visit 2 (-120 minutes)
measure: Blood pressure diastolic
timeFrame: At visit 2 (-120 minutes)
measure: Heart rate
timeFrame: At visit 2 (-120minutes)
Other outcomes:
measure: Changes in protein profiles
timeFrame: At visit 2 (60, 180, 300 minutes)
measure: Changes in metabolite profiles
timeFrame: At visit 2 (60, 180, 300 minutes)
Locations:
city: Basel
country: Switzerland
facility: University Hospital Basel
Study officials:
affiliation: University Hospital, Basel, Switzerland
name: Beckey Trinh, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: