A New Model of Acute Febrile Disease

University of Aarhus

Status: Completed

Conditions: Metabolism; Immobilization, Tonic; Endotoxemia; Fasting

Treatments: Other: LPS, 36 hour immobilization and fast

Study type: Interventional

Funder types: Other

Identifiers

NCT03158363

TheValidationStudy

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 6 patients

Sex: Male

Ages: 20 to 40 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Male sex
• 20 < BMI < 30
• 20 < Age < 40 years
• Written consent prior to trial

Exclusion criteria

• Participation in trials using ionized radiation a year prior to this trial.
• Comprehensive x-ray examinations in the study period.
• In case of immobilization of an extremity, the extremity should be fully re- habilitated and this should be stated by a physician or physiotherapist. The test subject's word for this will be sufficient.
• Allergies to eggs or soy oil.
• Diseases: Diabetes, epilepsy, ongoing infectious disease, immunodeficiency, heart disease, dysregulated hypertension.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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6 participants in 2 patient groups

"LPS, 36 hour immobilization and fast"

Experimental group

Description:

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.

Treatment:

Other: LPS, 36 hour immobilization and fast

"Control"

No Intervention group

Description:

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.