Lactate Metabolism After an Endotoxin Challenge in Healthy Humans

NCT01647997 | Completed

• 1 other identifier: Lsne-128/01
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

Sepsis is characterized by hyperlactatemia, the severity of which is proportionate with sepsis severity. The pathophysiological mechanisms (increased lactate production vs decreased lactate utilization; tissues involved in sepsis-induced lactate production) remain largely unknown. In this study, the investigators will assess whole body and regional metabolism in healthy young male subjects on two occasions, once after administration of an intravenous bacterial endotoxin challenge, and once without intervention. In one group of subjects, whole body lactate metabolism will be measured over 10 hours after the endotoxin challenge

• Energy expenditure and net substrate oxidation rates (indirect calorimetry)
• Lactate kinetics (measured by means of a continuous, exogenous sodium lactate infusion)
• Glucose kinetics (measured with 6,6 d2 glucose)
• Hemodynamic parameters and body temperature
• Blood clinical chemistry In one group of subjects, whole body lactate metabolism will be measured over 10 hours after the endotoxin challenge
• Energy expenditure and net substrate oxidation rates (indirect calorimetry)
• Lactate kinetics (measured by means of a continuous, exogenous sodium lactate infusion)
• Glucose kinetics (measured with 6,6 d2 glucose)
• Hemodynamic parameters and body temperature
• Blood clinical chemistry In a second group of subjects, regional muscle lactate metabolism will be measured over 10 hours after the endotoxin challenge by means of muscle microdialysis

Conditions

Sepsis

Keywords

bacterial lipopolysaccharides; hyperlactatemia; muscle lactate

Outcome Measures

Primary Outcomes (2)

• Whole body lactate production

  Whole body lactate clearance will be measured by measuring the increase in blood lactate at steady state during a conrtinuous exogenous sodium lactate infusion. Lactate production will be calculated as the product of lactate clearance times per-infusion blood lactate concentration

  single bacterial endotoxin administration; measurements over 6.5 hours following administration

• skeletal muscle lactate concentration

  interstitial muscle measured by means of in vivo microdialysis ; calculation of muscle-blood lactate gradient

  single bacterial endotoxin administration; measurements over 6.5 hours following administration

Secondary Outcomes (2)

• whole body energy expenditure

  single bacterial endotoxin administration; measurements over 6.5 hours following administration

• body temperature

  single bacterial endotoxin administration; measurements over 6.5 hours following administration

Study Arms (4)

study 1a

EXPERIMENTAL

whole body lactate production after bacterial endotoxin challenge

Other: bacterial endotoxin challenge

study 1b

NO INTERVENTION

basal whole body lactate production

study 2a

EXPERIMENTAL

muscle lactate concentration after bacterial endotoxin challenge

Other: bacterial endotoxin challenge

study 2b

NO INTERVENTION

basal muscle lactate concentrations

Interventions

bacterial endotoxin challenge OTHER

iv administration of 2ng/kg bacterial endotoxin

study 1a; study 2a

Eligibility Criteria

• Age: 18 Years - 30 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• gender male
• body mass index (BMI) \< 25 kg/m2
• absence of known disease

You may not qualify if:

• any known pathology
• abnormal cardio-pulmonary and hemodynamic status
• electrocardiographic alterations
• history of allergy
• current medications
• drug abuse
• consumption of more than 20g/day alcohol

Sponsors & Collaborators

• University of Lausanne: lead
• Centre Hospitalier Universitaire Vaudois: collaborator

Study Sites (1)

Centre Hospitalier Universitaire Vaudois

Lausanne, Canton of Vaud, CH-1011, Switzerland

Location

Related Publications (1)

• Michaeli B, Martinez A, Revelly JP, Cayeux MC, Chiolero RL, Tappy L, Berger MM. Effects of endotoxin on lactate metabolism in humans. Crit Care. 2012 Jul 27;16(4):R139. doi: 10.1186/cc11444.

  PMID: 22839504 DERIVED

MeSH Terms

Conditions

Sepsis; Hyperlactatemia

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Metabolic Diseases; Nutritional and Metabolic Diseases; Signs and Symptoms

Study Officials

• René Chiolero, MD

  Centre Hospitalier Universitaire Vaudois

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Physiology

Study Record Dates

• First Submitted: July 17, 2012
• First Posted: July 24, 2012
• Study Start: April 1, 2002
• Primary Completion: March 1, 2004
• Study Completion: December 1, 2004
• Last Updated: July 24, 2012

Record last verified: 2012-07

Locations

CH (1)