Back to results

A New Model of Acute Febrile Disease

Primary Purpose

Immobilization, Tonic, Fasting, Endotoxemia

Status

Completed

Phase

Not Applicable

Locations

Denmark

Study Type

Interventional

Intervention

LPS, 36 hour immobilization and fast

About this trial

This is an interventional basic science trial for Immobilization, Tonic focused on measuring immobilization, fasting, endotoxemia, LPS, metabolism, model of disease

Eligibility Criteria

20 Years - 40 Years (Adult)MaleAccepts 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.

Sites / Locations

Institute for Clinical MEdicine

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

"LPS, 36 hour immobilization and fast"

"Control"

Arm 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.

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.

Outcomes

Primary Outcome Measures

insulin sensitivity

Measured by hyperinsulinemic euglycemic clamp technique

Secondary Outcome Measures

Protein metabolism

Quantified by phenylalanine and tyrosine tracer methodology (whole body and the forearm model)

ketone body metabolic changes

measurement of ketone bodies

inflammation

Quantified by C-reactive peptide (CRP), white blood cell count, cytokines

Intracellular signalling pathway activation

Intracellular signalling pathway activation in muscle and fat

Energy expenditure

measured by indirect calorimetry

Glucose metabolism

measured by glucose tracer, calculations of rate of appearance, disappearance and endogenous glucose production

Hormonal changes

measures of insulin, glucagon, c-peptide and growth hormone

CD163

measures of CD163 and soluble CD163 (sCD163) after LPS exposure

Fat metabolism

measured by palmitate tracer, calculating whole body palmitate flux. Measures of free fatty acids.

Urea balance

measured by urea tracer and urine nitrogen excretion.

Glucose uptake by the forearm

Arterio-venous balance x blodflow

Full Information

NCT ID

NCT03158363

First Posted

May 16, 2017

Last Updated

February 20, 2019

Sponsor

University of Aarhus

Collaborators

Arla

1. Study Identification

Unique Protocol Identification Number

NCT03158363

Brief Title

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

2. Study Status

Record Verification Date

May 2017

Overall Recruitment Status

Completed

Study Start Date

June 1, 2017 (Actual)

Primary Completion Date

August 31, 2017 (Actual)

Study Completion Date

August 31, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Aarhus

Collaborators

Arla

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Immobilization, Tonic, Fasting, Endotoxemia, Metabolism

Keywords

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

7. Study Design

Primary Purpose

Basic Science

Study Phase

Not Applicable

Interventional Study Model

Crossover Assignment

Model Description

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

Masking

None (Open Label)

Allocation

Randomized

Enrollment

6 (Actual)

8. Arms, Groups, and Interventions

Arm Title

"LPS, 36 hour immobilization and fast"

Arm Type

Experimental

Arm Description

Arm Title

"Control"

Arm Type

No Intervention

Arm Description

Intervention Type

Other

Intervention Name(s)

LPS, 36 hour immobilization and fast

Intervention Description

LPS endotoxin is administered on study day 1 and immobilization and fast continue throughout study day 1 and 2.

Primary Outcome Measure Information:

Title

insulin sensitivity

Description

Measured by hyperinsulinemic euglycemic clamp technique

Time Frame

After a 3 hour clamp

Secondary Outcome Measure Information:

Title

Protein metabolism

Description

Quantified by phenylalanine and tyrosine tracer methodology (whole body and the forearm model)

Time Frame

measured at baseline and after 3 hours of clamp

Title

ketone body metabolic changes

Description

measurement of ketone bodies

Time Frame

measured at baseline and after 3 hours of clamp

Title

inflammation

Description

Quantified by C-reactive peptide (CRP), white blood cell count, cytokines

Time Frame

measurements over 36 hours

Title

Intracellular signalling pathway activation

Description

Intracellular signalling pathway activation in muscle and fat

Time Frame

measured at baseline and after 3 hours of clamp

Title

Energy expenditure

Description

measured by indirect calorimetry

Time Frame

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

Title

Glucose metabolism

Description

measured by glucose tracer, calculations of rate of appearance, disappearance and endogenous glucose production

Time Frame

measured at baseline and after 3 hours of clamp

Title

Hormonal changes

Description

measures of insulin, glucagon, c-peptide and growth hormone

Time Frame

measured at baseline and after 3 hours of clamp

Title

CD163

Description

measures of CD163 and soluble CD163 (sCD163) after LPS exposure

Time Frame

0, 24 and 48 hours after LPS exposure

Title

Fat metabolism

Description

measured by palmitate tracer, calculating whole body palmitate flux. Measures of free fatty acids.

Time Frame

measured at baseline and after 3 hours of clamp

Title

Urea balance

Description

measured by urea tracer and urine nitrogen excretion.

Time Frame

measured at baseline and after 3 hours of clamp

Title

Glucose uptake by the forearm

Description

Arterio-venous balance x blodflow

Time Frame

measured at baseline and after 3 hours of clamp

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

20 Years

Maximum Age & Unit of Time

40 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Niels Moeller, Professor

Organizational Affiliation

Institute for Clinical Medicine

Official's Role

Principal Investigator

Facility Information:

Facility Name

Institute for Clinical MEdicine

City

Aarhus

ZIP/Postal Code

8000

Country

Denmark

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

A New Model of Acute Febrile Disease

We'll reach out to this number within 24 hrs