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| Name | Class |
|---|---|
| Arla Foods | INDUSTRY |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| "LPS, 36 hour immobilization and fast" | Experimental | 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:
Study day 3: - Blood sample. |
|
| "Control" | No Intervention | Test subjects undergo overnight fast. No exercise restrictions.
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| LPS, 36 hour immobilization and fast | Other | LPS endotoxin is administered on study day 1 and immobilization and fast continue throughout study day 1 and 2. |
|
| Measure | Description | Time Frame |
|---|---|---|
| insulin sensitivity | Measured by hyperinsulinemic euglycemic clamp technique | After a 3 hour clamp |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Niels Moeller, Professor | Institute for Clinical Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Institute for Clinical MEdicine | Aarhus | 8000 | Denmark |
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| ID | Term |
|---|---|
| D046353 | Immobility Response, Tonic |
| D005215 | Fasting |
| D019446 | Endotoxemia |
| ID | Term |
|---|---|
| D001522 | Behavior, Animal |
| D001519 | Behavior |
| D009043 | Motor Activity |
| D005247 | Feeding Behavior |
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| ID | Term |
|---|---|
| D008070 | Lipopolysaccharides |
| D007103 | Immobilization |
| ID | Term |
|---|---|
| D006001 | Glycoconjugates |
| D002241 | Carbohydrates |
| D011135 | Polysaccharides, Bacterial |
| D011134 | Polysaccharides |
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Healthy young adults will be randomized to either intervention "Endotoxemia, 36 hour immobilization and fasting" or "overnight fast" being the control day.
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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 |
| D016470 |
| Bacteremia |
| D018805 | Sepsis |
| D007239 | Infections |
| D014115 | Toxemia |
| D018746 | Systemic Inflammatory Response Syndrome |
| D007249 | Inflammation |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D008055 |
| Lipids |
| D000942 | Antigens, Bacterial |
| D000941 | Antigens |
| D001685 | Biological Factors |
| D004731 | Endotoxins |
| D001427 | Bacterial Toxins |
| D014118 | Toxins, Biological |
| D008919 | Investigative Techniques |