Lactate Metabolism After an Endotoxin Challenge in Healthy Humans

This study has been completed.
Sponsor:
Collaborator:
Centre Hospitalier Universitaire Vaudois
Information provided by (Responsible Party):
Luc Tappy, MD, University of Lausanne
ClinicalTrials.gov Identifier:
NCT01647997
First received: July 17, 2012
Last updated: July 19, 2012
Last verified: July 2012
  Purpose

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


Condition Intervention
Sepsis
Other: bacterial endotoxin challenge

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Effects of an Acute Administration of Bacterial Endotoxin on Whole Body and Regional Lactate Metabolism in Healthy Male Volunteers

Resource links provided by NLM:


Further study details as provided by University of Lausanne:

Primary Outcome Measures:
  • Whole body lactate production [ Time Frame: single bacterial endotoxin administration; measurements over 6.5 hours following administration ] [ Designated as safety issue: No ]

    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


  • skeletal muscle lactate concentration [ Time Frame: single bacterial endotoxin administration; measurements over 6.5 hours following administration ] [ Designated as safety issue: No ]
    interstitial muscle measured by means of in vivo microdialysis ; calculation of muscle-blood lactate gradient


Secondary Outcome Measures:
  • whole body energy expenditure [ Time Frame: single bacterial endotoxin administration; measurements over 6.5 hours following administration ] [ Designated as safety issue: No ]
    open circuit indirect calorimetry (hood)

  • body temperature [ Time Frame: single bacterial endotoxin administration; measurements over 6.5 hours following administration ] [ Designated as safety issue: No ]

Enrollment: 14
Study Start Date: April 2002
Study Completion Date: December 2004
Primary Completion Date: March 2004 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: study 1a
whole body lactate production after bacterial endotoxin challenge
Other: bacterial endotoxin challenge
iv administration of 2ng/kg bacterial endotoxin
No Intervention: study 1b
basal whole body lactate production
Experimental: study 2a
muscle lactate concentration after bacterial endotoxin challenge
Other: bacterial endotoxin challenge
iv administration of 2ng/kg bacterial endotoxin
No Intervention: study 2b
basal muscle lactate concentrations

  Eligibility

Ages Eligible for Study:   18 Years to 30 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

  • 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01647997

Locations
Switzerland
Centre Hospitalier Universitaire Vaudois
Lausanne, Vaud, Switzerland, CH-1011
Sponsors and Collaborators
University of Lausanne
Centre Hospitalier Universitaire Vaudois
Investigators
Principal Investigator: René Chiolero, MD Centre Hospitalier Universitaire Vaudois
  More Information

No publications provided

Responsible Party: Luc Tappy, MD, Professor of Physiology, University of Lausanne
ClinicalTrials.gov Identifier: NCT01647997     History of Changes
Other Study ID Numbers: Lsne-128/01
Study First Received: July 17, 2012
Last Updated: July 19, 2012
Health Authority: Switzerland: Ethikkommission

Keywords provided by University of Lausanne:
bacterial lipopolysaccharides
hyperlactatemia
muscle lactate

Additional relevant MeSH terms:
Sepsis
Infection
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes

ClinicalTrials.gov processed this record on April 21, 2014