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InflammationNCT01452958

Endotoxin & Cytokines. Do Protein Loss and Metabolic Effects Depend on Central Nervous System (CNS) Activation of Stress Hormones or on Local Mechanisms in Muscle and Fat?

A study testing TNF-alpha and Endotoxin in people with Inflammation and Glucose Metabolism Disorders, run by Aarhus University Hospital at 1 site in Denmark.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Main objective : The purpose of this study is to prove that the effects of bacterial endotoxin and cytokine TNF-α, on protein loss, fatty acid release, and glucose metabolism depend on two mechanisms: 1. Direct local effects in muscle tissue. 2. Read more about this study

Who is it for?
Ages 18 to 70 years, men onlyHealthy volunteers can take part
Conditions the study is for
Inflammation, Glucose Metabolism Disorders
What is being tested?
TNF-alpha and Endotoxin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
1 siteDenmark
Study dates
Jun 2010to Jan 2013
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 18 to 70 years
  • Men only
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Male
  • 19 < BMI < 28
  • 18 ≤ Age ≤ 50
  • Healthy
  • Male
  • 20 < BMI < 30
  • Age > 25
  • Healthy

Who cannot join

  • Diseases
  • Allergy

Trial locations and contacts

1 site in 1 country.

Denmark1 site

  • Medical Department MEA, NBG, Aarhus University Hospital

    Aarhus, 8000

Other trials in Denmark

About this study

Official title: Endotoxin & Cytokines. Do Protein Loss and Metabolic Effects Depend on CNS Activation of Stress Hormones or on Local Mechanisms in Muscle and Fat?

Main objective :

The purpose of this study is to prove that the effects of bacterial endotoxin and cytokine TNF-α, on protein loss, fatty acid release, and glucose metabolism depend on two mechanisms:

Read more
  1. Direct local effects in muscle tissue.
  2. Activation of the hypothalamo-pituitary axis and a stress-hormone response

Study protocols:

  1. Acute metabolic effects of TNF-α(Beromun, Boehringer-Ingelheim Germany) vs placebo perfused into the femoral artery of the leg in 8 healthy subjects.
  2. Acute metabolic effects of
  • placebo(saline)
  • endotoxin(US standard reference E.Coli, endotoxin)
  • TNF-α(Beromun, Boehringer-Ingelheim Germany) given systemically
  • in 8 patients with hypopituitarism(to block stress hormone release) and in 8 healthy subjects all studied thrice.
Read the detailed description

PURPOSE:

Knowledge about the effects of bacterial endotoxin and cytokines (and inflammation in general) in humans on protein, glucose and lipid metabolism and intracellular signalling in muscle and fat is sporadic and it is uncertain whether endotoxin and cytokines act directly in fat and muscle tissue or indirectly via central nervous system (CNS) mediated stress hormone release.

The investigators hypothesize that the metabolic effects of endotoxin and cytokine TNF-α, including protein loss, fatty acid release and decreased glucose uptake depend on two mechanisms:

  1. Direct local effects in muscle tissue (Study protocol 1)
  2. Activation of the hypothalamo-pituitary axis and generalized stress hormone response (Study protocol 2)

METHODOLOGY:

Study protocol 1:

Acute metabolic effects of TNF-α (Beromun, Boehringer-Ingelheim, Germany) versus placebo perfused into the femoral artery of the leg in 8 healthy subjects, studied once. Femoral vein sampling allows assessment of local metabolic events in the leg. The vessels were cannulated using the Seldinger technique. Each study comprises a 3 hour basal period and a 3 hour Hyperinsulinemic-Euglycemic Clamp. Muscle biopsies were obtained simultaneously from both lateral vastus muscles.

Study protocol 2:

Acute metabolic effects of (i)placebo (saline), (ii)endotoxin (US standard reference E.Coli, endotoxin) and (iii)TNF-α (Beromun, Boehringer-Ingelheim, Germany) given systemically intravenously (i.v.) in 8 patients with hypopituitarism (to block stress hormone release) and in 8 healthy subjects all studied thrice. Every study comprises a 4 hour basal period and a 2 hour Hyperinsulinemic-Euglycemic Clamp. Muscle and fat biopsies were obtained.

Study protocol 1 and Study protocol 2:

Assays: Mass spectrometry (15N-phenylalanine, 13C-urea), 3H-glucose, 3H-palmitate quantification, hormone and metabolite analysis, cytokine assays, intracellular signaling.

Being tested
TNF-alpha, Endotoxin
Keywords
Endotoxin, LPS, TNF-α, insulin resistance, metabolism
Medical subject headings
Inflammation, Glucose Metabolism Disorders, Insulin Resistance

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TNF-alphaBiological

    Also called Beromun, Boehringer-Ingelheim, Germany

    Study protocol 1: 6 ng/kg/h intraarterial Study protocol 2: 18 ng/kg/h intravenous

  • EndotoxinBiological

    Also called E. coli endotoxin, US standard

    Study protocol 2:0,075 ng/kg/h intravenous

Study groups in NCT01452958
Study groupRoleWhat they receive
TNF-αExperimentalBeromun, Boehringer-Ingelheim, Germany
Receives: Biological: TNF-alpha
EndotoxinExperimentalNot described
Receives: Biological: Endotoxin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Acute metabolic effects of endotoxin and cytokine TNF-α (Study 2)

    During a basal period.

    Acute metabolic effects: Glucose metabolism was quantified with raw arterio-venous differences and 3H3-Glucose tracer. Lactate was quantified with raw arterio-venous differences. Lipid metabolism was quantified with [9,10-3H]-Palmitate tracer and amino acid metabolism with 15N-Phenylalanine tracer and 13C-Urea tracer.

    Measured: 2 hours

  2. Acute metabolic effects of endotoxin and cytokine TNF-α (Study 2)

    During a hyperinsulinaemic euglycaemic clamp.

    Acute metabolic effects: Glucose metabolism was quantified with raw arterio-venous differences and 3H3-Glucose tracer. Lactate was quantified with raw arterio-venous differences. Lipid metabolism was quantified with [9,10-3H]-Palmitate tracer and amino acid metabolism with 15N-Phenylalanine tracer and 13C-Urea tracer.

    Measured: 4 hours

  3. Acute metabolic effects of cytokine TNF-α (Study 1)

    During a basal period.

    Acute metabolic effects: Glucose and lactate were quantified with raw arterio-venous differences; lipid metabolism was quantified with [9,10-3H]-palmitate and amino acid metabolism with 15N-phenylalanine.

    Measured: 3 hours

  4. Acute metabolic effects of cytokine TNF-α (Study 1)

    During a hyperinsulinaemic euglycaemic clamp.

    Acute metabolic effects: Glucose and lactate were quantified with raw arterio-venous differences; lipid metabolism was quantified with [9,10-3H]-palmitate and amino acid metabolism with 15N-phenylalanine.

    Measured: 3 hours

Secondary outcomes (2)

  1. Intracellular insulin signaling, growth hormone signalling and inflammatory signalling pathways.

    Musle and fat biopsies during a basal period (120 min. from the beginning of a basal period)

    Measured: 120 min.

  2. Intracellular insulin signaling, growth hormone signalling and inflammatory signalling pathways.

    Musle and fat biopsies during a hyperinsulinaemic euglycaemic clamp (30 min. from the beginning of clamp)

    Measured: 30 min.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Oct 2011 (estimated)
  2. Study startJun 2010
  3. Primary completionJan 2013
  4. Study completionJan 2013

Resources

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
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Care provider
Enrolment
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01452958
Sponsor's protocol ID
2010/0604
Status last verified
Jan 2013
First submitted
22 Sep 2011
Last updated
30 Jan 2013
Results posted
No
Data monitoring committee
Yes

Publications

  • Bach E, Nielsen RR, Vendelbo MH, Moller AB, Jessen N, Buhl M, K-Hafstrom T, Holm L, Pedersen SB, Pilegaard H, Bienso RS, Jorgensen JO, Moller N. Direct effects of TNF-alpha on local fuel metabolism and cytokine levels in the placebo-controlled, bilaterally infused human leg: increased insulin sensitivity, increased net protein breakdown, and increased IL-6 release. Diabetes. 2013 Dec;62(12):4023-9. doi: 10.2337/db13-0138. Epub 2013 Jul 8.

    PubMed 23835341

Questions about this trial

What is this clinical trial studying?

A study testing TNF-alpha and Endotoxin in people with Inflammation and Glucose Metabolism Disorders, run by Aarhus University Hospital 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 8 inclusion and 2 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 30 Jan 2013. 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?

Acute metabolic effects of endotoxin and cytokine TNF-α (Study 2) (time frame: 2 hours). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01452958, which also lists 1 linked publication.

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 30 Jan 2013.

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