An interventional study of LPS, 36 hour immobilization and fast in Immobilization, Tonic, Fasting and Endotoxemia, sponsored by University of Aarhus. Completed at 1 site in Denmark. Open to male participants aged 20 Years to 40 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2019-02-22.
Sponsored by University of Aarhus · Not applicable, Interventional, and Basic science
The investigators want to establish a new model of acute febrile disease by mimicking the conditions seen in hospitalized patients in regards to inflammation, immobilisation and fasting. In this new model of disease, healthy young adults will be given lipopolysaccharide (LPS) to induce endotoxemia and inflammation/fever and then fast and bedrest for 36 hours. Glucose, fat and protein metabolism will be investigated using clamp technique and tracer methodology together with intracellular signalling pathway activation in muscle and fat biopsies. This new model of disease will later be used in another study to investigate different protein supplement´s effect on muscle waste during acute febrile disease.
The investigators want to establish a new model of acute febrile disease by mimicking the conditions seen in hospitalized patients in regards to inflammation, immobilisation and fasting. In this new model of disease, healthy young adults will be given lipopolysaccharide (LPS) to induce endotoxemia and inflammation on study day 1 and then fast and bedrest for 36 hours (Study day 2). Glucose, fat and protein metabolism will be investigated using clamp technique and tracer methodology together with intracellular signalling pathway activation in muscle and fat biopsies. This new model of disease will later be used in another study to investigate different protein supplement´s effect on muscle waste during acute febrile disease.
Exclusion Criteria:
Interventions: Test subjects undergo 48 hour exercise restriction and overnight fast. Study day 1: - LPS (1 ng/kg) will be administered. Test subjects will fast and bedrest for the rest of the study period. Study day 2: * 3 hour Basal period: Continued fast and bedrest. Phenylalanine, tyrosine, carbamide, glucose and palmitate tracers are infused. Muscle and fat biopsies are taken from m. vastus lateralis and stomach. * 3 hour hyperinsulinemic euglycemic clamp period with muscle and fat biopsies. Study day 3: - Blood sample.
Other: LPS, 36 hour immobilization and fast
Test subjects undergo overnight fast. No exercise restrictions. * 3 hour Basal period: Continued fast and bedrest. Phenylalanine, tyrosine, carbamide, glucose and palmitate tracers are infused. Muscle and fat biopsies are taken from m. vastus lateralis and stomach. * 3 hour hyperinsulinemic euglycemic clamp period with muscle and fat biopsies.
LPS endotoxin is administered on study day 1 and immobilization and fast continue throughout study day 1 and 2.
insulin sensitivity
Measured by hyperinsulinemic euglycemic clamp technique
Time frame: After a 3 hour clamp
Protein metabolism
Quantified by phenylalanine and tyrosine tracer methodology (whole body and the forearm model)
Time frame: measured at baseline and after 3 hours of clamp
ketone body metabolic changes
measurement of ketone bodies
Time frame: measured at baseline and after 3 hours of clamp
inflammation
Quantified by C-reactive peptide (CRP), white blood cell count, cytokines
Time frame: measurements over 36 hours
Intracellular signalling pathway activation
Intracellular signalling pathway activation in muscle and fat
Time frame: measured at baseline and after 3 hours of clamp
Energy expenditure
measured by indirect calorimetry
Time frame: measured at baseline and after 3 hours of clamp for 15 minutes
Glucose metabolism
measured by glucose tracer, calculations of rate of appearance, disappearance and endogenous glucose production
Time frame: measured at baseline and after 3 hours of clamp
Hormonal changes
measures of insulin, glucagon, c-peptide and growth hormone
Time frame: measured at baseline and after 3 hours of clamp
CD163
measures of CD163 and soluble CD163 (sCD163) after LPS exposure
Time frame: 0, 24 and 48 hours after LPS exposure
Fat metabolism
measured by palmitate tracer, calculating whole body palmitate flux. Measures of free fatty acids.
Time frame: measured at baseline and after 3 hours of clamp
Urea balance
measured by urea tracer and urine nitrogen excretion.
Time frame: measured at baseline and after 3 hours of clamp
Glucose uptake by the forearm
Arterio-venous balance x blodflow
Time frame: measured at baseline and after 3 hours of clamp
Plan to share: No
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University of Aarhus