A New Model of Acute Febrile Disease

A New Model of Acute Febrile Disease - Combining Endotoxemia, Immobilisation and Fasting in Healthy Young Males.

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.

Study Overview

• Status: Completed
• Conditions: Endotoxemia; Fasting; Metabolism; Immobilization, Tonic
• Intervention / Treatment: Other: LPS, 36 hour immobilization and fast

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.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Aarhus, Denmark, 8000
    • Institute for clinical Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: "LPS, 36 hour immobilization and fast"; 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; LPS endotoxin is administered on study day 1 and immobilization and fast continue throughout study day 1 and 2.
No Intervention: "Control"; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
insulin sensitivity	Measured by hyperinsulinemic euglycemic clamp technique	After a 3 hour clamp

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Protein metabolism	Quantified by phenylalanine and tyrosine tracer methodology (whole body and the forearm model)	measured at baseline and after 3 hours of clamp
ketone body metabolic changes	measurement of ketone bodies	measured at baseline and after 3 hours of clamp
inflammation	Quantified by C-reactive peptide (CRP), white blood cell count, cytokines	measurements over 36 hours
Intracellular signalling pathway activation	Intracellular signalling pathway activation in muscle and fat	measured at baseline and after 3 hours of clamp
Energy expenditure	measured by indirect calorimetry	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	measured at baseline and after 3 hours of clamp
Hormonal changes	measures of insulin, glucagon, c-peptide and growth hormone	measured at baseline and after 3 hours of clamp
CD163	measures of CD163 and soluble CD163 (sCD163) after LPS exposure	0, 24 and 48 hours after LPS exposure
Fat metabolism	measured by palmitate tracer, calculating whole body palmitate flux. Measures of free fatty acids.	measured at baseline and after 3 hours of clamp
Urea balance	measured by urea tracer and urine nitrogen excretion.	measured at baseline and after 3 hours of clamp
Glucose uptake by the forearm	Arterio-venous balance x blodflow	measured at baseline and after 3 hours of clamp

Collaborators and Investigators

• Sponsor: University of Aarhus
• Collaborators: Arla
• Investigators: Principal Investigator: Niels Moeller, Professor, Institute for clinical Medicine

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2017
• Primary Completion (Actual): August 31, 2017
• Study Completion (Actual): August 31, 2017

Study Registration Dates

• First Submitted: May 16, 2017
• First Submitted That Met QC Criteria: May 16, 2017
• First Posted (Actual): May 18, 2017

Study Record Updates

• Last Update Posted (Actual): February 22, 2019
• Last Update Submitted That Met QC Criteria: February 20, 2019
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: LPS; metabolism; fasting; immobilization; endotoxemia; model of disease
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Bacteremia; Toxemia; Endotoxemia
• Other Study ID Numbers: TheValidationStudy

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No