Clinical trial NCT03158363: A New Model of Acute Febrile Disease
Official title: A New Model of Acute Febrile Disease - Combining Endotoxemia, Immobilisation and Fasting in Healthy Young Males.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Immobilization, Tonic
Fasting
Endotoxemia
Metabolism
Keywords: immobilization
fasting
endotoxemia
LPS
metabolism
model of disease
Lead sponsor: University of Aarhus
Sponsor class: OTHER
Collaborators: name: Arla
First posted: 2017-05-18
Enrollment: 6
Sex: MALE
Minimum age (years): 20
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Healthy young adults will be randomized to either intervention "Endotoxemia, 36 hour immobilization and fasting" or "overnight fast" being the control day.
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: insulin sensitivity
timeFrame: After a 3 hour clamp
Secondary outcomes:
measure: Protein metabolism
timeFrame: measured at baseline and after 3 hours of clamp
measure: ketone body metabolic changes
timeFrame: measured at baseline and after 3 hours of clamp
measure: inflammation
timeFrame: measurements over 36 hours
measure: Intracellular signalling pathway activation
timeFrame: measured at baseline and after 3 hours of clamp
measure: Energy expenditure
timeFrame: measured at baseline and after 3 hours of clamp for 15 minutes
measure: Glucose metabolism
timeFrame: measured at baseline and after 3 hours of clamp
measure: Hormonal changes
timeFrame: measured at baseline and after 3 hours of clamp
measure: CD163
timeFrame: 0, 24 and 48 hours after LPS exposure
measure: Fat metabolism
timeFrame: measured at baseline and after 3 hours of clamp
measure: Urea balance
timeFrame: measured at baseline and after 3 hours of clamp
measure: Glucose uptake by the forearm
timeFrame: measured at baseline and after 3 hours of clamp
Other outcomes:
Locations:
city: Aarhus
country: Denmark
facility: Institute for Clinical MEdicine
Study officials:
affiliation: Institute for Clinical Medicine
name: Niels Moeller, Professor
role: PRINCIPAL_INVESTIGATOR
References: