Immobilization, TonicNCT03158363
A New Model of Acute Febrile Disease
A study testing LPS, 36 hour immobilization and fast in people with Immobilization, Tonic and Fasting, run by University of Aarhus at 1 site in Denmark.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 to 40 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Immobilization, Tonic, Fasting, Endotoxemia
- What is being tested?
- LPS, 36 hour immobilization and fast
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteDenmark
- Study dates
- 1 Jun 2017to 31 Aug 2017
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 40 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Male sex
- 20 < BMI < 30
- 20 < Age < 40 years
- Written consent prior to trial
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Conditions
- Immobilization, Tonic, Fasting, Endotoxemia, Metabolism
- Being tested
- LPS, 36 hour immobilization and fast
- Keywords
- immobilization, fasting, endotoxemia, LPS, metabolism, model of disease
- Medical subject headings
- Immobility Response, Tonic, Fasting, Endotoxemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LPS, 36 hour immobilization and fastOther
LPS endotoxin is administered on study day 1 and immobilization and fast continue throughout study day 1 and 2.
| Study group | Role | What they receive |
|---|---|---|
| "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. Receives: 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
insulin sensitivity
Measured by hyperinsulinemic euglycemic clamp technique
Measured: After a 3 hour clamp
Secondary outcomes (11)
Protein metabolism
Quantified by phenylalanine and tyrosine tracer methodology (whole body and the forearm model)
Measured: measured at baseline and after 3 hours of clamp
ketone body metabolic changes
measurement of ketone bodies
Measured: measured at baseline and after 3 hours of clamp
inflammation
Quantified by C-reactive peptide (CRP), white blood cell count, cytokines
Measured: measurements over 36 hours
Intracellular signalling pathway activation
Intracellular signalling pathway activation in muscle and fat
Measured: measured at baseline and after 3 hours of clamp
Energy expenditure
measured by indirect calorimetry
Measured: 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: measured at baseline and after 3 hours of clamp
Hormonal changes
measures of insulin, glucagon, c-peptide and growth hormone
Measured: measured at baseline and after 3 hours of clamp
CD163
measures of CD163 and soluble CD163 (sCD163) after LPS exposure
Measured: 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: measured at baseline and after 3 hours of clamp
Urea balance
measured by urea tracer and urine nitrogen excretion.
Measured: measured at baseline and after 3 hours of clamp
Glucose uptake by the forearm
Arterio-venous balance x blodflow
Measured: measured at baseline and after 3 hours of clamp
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 May 2017
- Study start1 Jun 2017
- Primary completion31 Aug 2017
- Study completion31 Aug 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Immobilization, TonicStudies of the same condition, open and under way.
- More trials run by University of AarhusThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- 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)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Aarhus
- Sponsor type
- University, hospital or other
- Collaborators
- Arla Foods
- Responsible party
- Sponsor
- Investigators
- Niels Moeller, Professor, Principal investigator, Institute for Clinical Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03158363
- Sponsor's protocol ID
- TheValidationStudy
- Status last verified
- May 2017
- First submitted
- 16 May 2017
- Last updated
- 22 Feb 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A New Model of Acute Febrile Disease - Combining Endotoxemia, Immobilisation and Fasting in Healthy Young Males.
- ClinicalTrials.gov ID
- NCT03158363
- Acronym / sponsor ID
- TheValidationStudy
- Conditions
- Immobilization, Tonic, Fasting, Endotoxemia, Metabolism
- Keywords
- immobilization, fasting, endotoxemia, LPS, metabolism, model of disease
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- University of AarhusUniversity, hospital or other
- Collaborators
- Arla Foods
- Study start
- 1 Jun 2017 (actual)
- Primary completion
- 31 Aug 2017 (actual)
- Study completion
- 31 Aug 2017 (actual)
- First posted
- 18 May 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Healthy young adults will be randomized to either intervention "Endotoxemia, 36 hour immobilization and fasting" or "overnight fast" being the control day.
| Arm | Type | Receives |
|---|---|---|
| "LPS, 36 hour immobilization and fast" | Experimental | Other: LPS, 36 hour immobilization and fastInterventions: 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. |
| "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. |
Who may qualify
- Ages
- 20 to 40 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Male sex
- 20 < BMI < 30
- 20 < Age < 40 years
- Written consent prior to trial
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LPS, 36 hour immobilization and fastLPS endotoxin is administered on study day 1 and immobilization and fast continue throughout study day 1 and 2. | Other | "LPS, 36 hour immobilization and fast" |
Primary outcome
insulin sensitivity
Time frame: After a 3 hour clamp
Measured by hyperinsulinemic euglycemic clamp technique
11 secondary outcomes
Protein metabolism
Time frame: measured at baseline and after 3 hours of clamp
ketone body metabolic changes
Time frame: measured at baseline and after 3 hours of clamp
inflammation
Time frame: measurements over 36 hours
Intracellular signalling pathway activation
Time frame: measured at baseline and after 3 hours of clamp
Energy expenditure
Time frame: measured at baseline and after 3 hours of clamp for 15 minutes
Glucose metabolism
Time frame: measured at baseline and after 3 hours of clamp
Hormonal changes
Time frame: measured at baseline and after 3 hours of clamp
CD163
Time frame: 0, 24 and 48 hours after LPS exposure
Fat metabolism
Time frame: measured at baseline and after 3 hours of clamp
Urea balance
Time frame: measured at baseline and after 3 hours of clamp
Glucose uptake by the forearm
Time frame: measured at baseline and after 3 hours of clamp
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Feb 2019.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Niels Moeller, Professor principal investigator
Institute for Clinical Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing LPS, 36 hour immobilization and fast in people with Immobilization, Tonic and Fasting, run by University of Aarhus at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
insulin sensitivity (time frame: After a 3 hour clamp). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Feb 2019.