Lactate Metabolism After an Endotoxin Challenge in Healthy Humans

Study Overview
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Brief Summary
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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

Official Title
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Effects of an Acute Administration of Bacterial Endotoxin on Whole Body and Regional Lactate Metabolism in Healthy Male Volunteers

Conditions
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Sepsis

Intervention / Treatment
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* Other: bacterial endotoxin challenge


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: study 1a<br>whole body lactate production after bacterial endotoxin challenge | Other: bacterial endotoxin challenge<br>* iv administration of 2ng/kg bacterial endotoxin<br>|
| No Intervention: study 1b<br>basal whole body lactate production | |
| Experimental: study 2a<br>muscle lactate concentration after bacterial endotoxin challenge | Other: bacterial endotoxin challenge<br>* iv administration of 2ng/kg bacterial endotoxin<br>|
| No Intervention: study 2b<br>basal muscle lactate concentrations | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| whole body energy expenditure | open circuit indirect calorimetry (hood) | single bacterial endotoxin administration; measurements over 6.5 hours following administration | 
| body temperature |  | single bacterial endotoxin administration; measurements over 6.5 hours following administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bacterial lipopolysaccharides, hyperlactatemia, muscle lactate