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?

NCT01452958 | Completed DMC

• 1 other identifier: 2010/0604
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief 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:

• 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.

Conditions

Inflammation; Glucose Metabolism Disorders

Keywords

Endotoxin; LPS; TNF-α; insulin resistance; metabolism

Outcome Measures

Primary Outcomes (4)

• 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.

  2 hours

• 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.

  4 hours

• 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.

  3 hours

• 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.

  3 hours

Secondary Outcomes (2)

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

  120 min.

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

  30 min.

Study Arms (2)

TNF-α

EXPERIMENTAL

Beromun, Boehringer-Ingelheim, Germany

Biological: TNF-alpha

Endotoxin

EXPERIMENTAL

Biological: Endotoxin

Interventions

TNF-alpha BIOLOGICAL

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

Also known as: Beromun, Boehringer-Ingelheim, Germany

TNF-α

Endotoxin BIOLOGICAL

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

Also known as: E. coli endotoxin, US standard

Endotoxin

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male
• \< BMI \< 28
• ≤ Age ≤ 50
• Healthy
• Male
• \< BMI \< 30
• Age \> 25
• Healthy

You may not qualify if:

• Diseases
• Allergy

Sponsors & Collaborators

• Aarhus University Hospital: lead
• University of Aarhus: collaborator
• Lundbeck Foundation: collaborator

Study Sites (1)

Medical Department MEA, NBG, Aarhus University Hospital

Aarhus, 8000, Denmark

Location

Related Publications (1)

• 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.

  PMID: 23835341 DERIVED

MeSH Terms

Conditions

Inflammation; Glucose Metabolism Disorders; Insulin Resistance

Interventions

Tumor Necrosis Factor-alpha; Endotoxins

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Metabolic Diseases; Nutritional and Metabolic Diseases; Hyperinsulinism

Intervention Hierarchy (Ancestors)

Glycoproteins; Glycoconjugates; Carbohydrates; Monokines; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Tumor Necrosis Factors; Blood Proteins; Proteins; Biological Factors; Bacterial Toxins; Toxins, Biological

Study Officials

• Niels Møller, Professor

  Aarhus University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Doctor, PhD student

Study Record Dates

• First Submitted: September 22, 2011
• First Posted: October 17, 2011
• Study Start: June 1, 2010
• Primary Completion: January 1, 2013
• Study Completion: January 1, 2013
• Last Updated: January 30, 2013

Record last verified: 2013-01

Locations

DK (1)