A New Model of Acute Febrile Disease

NCT03158363 | Completed

• 1 other identifier: TheValidationStudy
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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.

Conditions

Immobilization, Tonic; Fasting; Endotoxemia; Metabolism

Keywords

immobilization; fasting; endotoxemia; LPS; metabolism; model of disease

Outcome Measures

Primary Outcomes (1)

• insulin sensitivity

  Measured by hyperinsulinemic euglycemic clamp technique

  After a 3 hour clamp

Secondary Outcomes (11)

• Protein metabolism

  measured at baseline and after 3 hours of clamp

• ketone body metabolic changes

  measured at baseline and after 3 hours of clamp

• inflammation

  measurements over 36 hours

• Intracellular signalling pathway activation

  measured at baseline and after 3 hours of clamp

• Energy expenditure

  measured at baseline and after 3 hours of clamp for 15 minutes

Study Arms (2)

"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: * 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

"Control"

NO INTERVENTION

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.

Interventions

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.

"LPS, 36 hour immobilization and fast"

Eligibility Criteria

• Age: 20 Years - 40 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Aarhus: lead
• Arla: collaborator

Study Sites (1)

Institute for Clinical MEdicine

Aarhus, 8000, Denmark

Location

MeSH Terms

Conditions

Immobility Response, Tonic; Fasting; Endotoxemia

Interventions

Lipopolysaccharides; Immobilization

Condition Hierarchy (Ancestors)

Behavior, Animal; Behavior; Motor Activity; Feeding Behavior; Bacteremia; Sepsis; Infections; Toxemia; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Glycoconjugates; Carbohydrates; Polysaccharides, Bacterial; Polysaccharides; Lipids; Antigens, Bacterial; Antigens; Biological Factors; Endotoxins; Bacterial Toxins; Toxins, Biological; Investigative Techniques

Study Officials

• Niels Moeller, Professor

  Institute for Clinical Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Healthy young adults will be randomized to either intervention "Endotoxemia, 36 hour immobilization and fasting" or "overnight fast" being the control day.

Study Record Dates

• First Submitted: May 16, 2017
• First Posted: May 18, 2017
• Study Start: June 1, 2017
• Primary Completion: August 31, 2017
• Study Completion: August 31, 2017
• Last Updated: February 22, 2019

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)