Clinical Trial: Endotoxin-induced Inflammatory and Behavioral Responses and Predictors of Individual Differences

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Endotoxin-induced Inflammatory and Behavioral Responses and Predictors of Individual Differences: A Randomized, Double-blind Placebo Controlled Study on Healthy Human Volunteers

Brief Summary:

The objective of the present study is to specifically assess the effect of lipopolysaccharide (LPS) administration on the development of behavioral symptoms and the underlying contribution of inflammatory processes. In particular, the investigators will assess the development of subjective and objective behavioral symptoms. In addition, the investigators will determine whether some psychological trait or state can predict and/or modulate the LPS-induced inflammatory and behavioral responses.

Twenty-five healthy subjects will be included. A placebo-controlled, double-blinded and cross-over design will be used. Subjects will receive an intravenous injection of endotoxin at 2 nanogram/kilogram (ng/kg) of body weight and an intravenous injection of sodium chloride as placebo of endotoxin injection at two different occasions.

Prior to inclusion and randomization, subjects will come at the hospital and will receive a medical examination. Psychological variables that could affect the behavioral (or immune) response to LPS will be assessed at that time, using several self-assessment questionnaires.

On the trial days, injection of endotoxin or sodium chloride will be performed and blood samples will be taken just before the endotoxin or sodium chloride injection and 1, 1.5, 2, 3, 4, 5, 6 and 7.5 hours after the injection. Blood samples will be used to measure several inflammatory and immune markers. Urine samples will be taken before the endotoxin or sodium chloride injection and as late as possible after the injection. Subjects will wear T-shirt all day. Urine and T-shirt samples will be used for behavioral assessment and analysis of body odor compound.

Self-assessment questionnaires assessing behavioral and psychological variables

Detailed Summary:

Study design

Twenty-five subjects will be included in the present study, which will follow a prospective, placebo-controlled and cross-over design. Participants will be blinded, as well as research personnel in charge of the participants and the laboratory.

Subjects will be randomly assigned in the cross-over design with two trials, with about four weeks wash-out between LPS stimulations:

  1. Trial 1: endotoxin. Subjects will receive an intravenous injection of endotoxin at 2 ng/kg of body weight.
  2. Trial 2: placebo. Subjects will receive an intravenous injection of sodium chloride as placebo of endotoxin injection.

Ten other healthy volunteers will be recruited in a pilot study prior the beginning of the main study, in order to test the behavioral tasks that will be used. These subjects will be recruited among the university staff or among university students. They will perform four specific behavioral tasks and will complete the questionnaires assessing psychological and behavioral variables in order to associate outcomes from the behavioral tasks to psychological and subjective behavioral assessments. No biological samples (blood, urine or tee-shirt samples) will be taken in subjects recruited in the pilot study.

Treatment

The LPS is provided by LGC Promochem AB, Albanoliden 5, 4tr, 506 30 Borås, Sweden. The USP (United States Pharmacopeial Convention) Endotoxin (Cat. No. 1235503) does come as a lyophilized (freeze-dried) powder and each vial contains 10,000 USP Endotoxin Units. Each vial contains very approximately 1 microgram of Endotoxin and is mixe
Sponsor: Karolinska Institutet

Current Primary Outcome:

  • Change from baseline in sickness behavior as measured using the sicknessQ [ Time Frame: Before the administration and 1.5, 3, 5 and 7 hours after the administration ]
    Change in sickness behavior evaluated using the self-assessment questionnaire sicknessQ
  • Change from baseline in anxiety state as measured using the STAI-State [ Time Frame: Before the administration and 3 and 7 hours after the administration ]
    Change in symptoms of anxiety evaluated using the self-assessment questionnaire State part of the State-Trait Anxiety Inventory (STAI)
  • Change from baseline in psychological state as measured using the SCAS [ Time Frame: Before the administration and 3 and 7 hours after the administration ]
    Change in mood alterations evaluated using the self-assessment questionnaire Swedish Core Affect Scales (SCAS)
  • Change from baseline in pain as measured using the short McGill questionnaire [ Time Frame: Before the administration and 3 and 7 hours after the administration ]
    Change in symptoms of pain evaluated using the self-assessment questionnaire Mc Gill questionnaire - short version
  • Change from baseline in sleepiness as measured using the KSS [ Time Frame: Before the administration and 3 and 7 hours after the administration ]
    Change in sleepiness evaluated using the Karolinska Sleepiness Scale (KSS)
  • Change from baseline in systemic IL-6 concentrations [ Time Frame: Before the a

    Original Primary Outcome: Same as current

    Current Secondary Outcome:

    • Change in cell expression of blood microparticles [ Time Frame: Before the administration and 1, 1.5, 2, 3, 4, 5, 7 hours after the administration ]
      Changes in concentrations of total microparticles (defined as particles less than 1μm in size and staining for lactadherin) and platelet-, monocytes- and endothelial-derived microparticles (co-staining of lactadherin and, respectively, cluster of differentiation (CD)42A, CD14 and CD62E).
    • Modification in genetic markers [ Time Frame: Before the administration and 1, 2, 4, 7 hours after the administration ]
      Modification in genetic markers measured using CAGE analysis from PAXGene blood samples
    • Change in expression of immune cell markers [ Time Frame: Before the administration and 1, 2, 3, 4, 7 hours after the administration ]
      Change in expression of immune cell subpopulations markers using flow cytometry from frozen whole blood in 10% Dimethylsulfoxid (DMSO)
    • Change in odor compounds [ Time Frame: Before and after the administration ]
      Change in abundance of volatile odor compounds analyzed using gas chromatography mass spectrometry (GC-MS) from tee-shirt samples and urine samples
    • Changes in social interaction [ Time Frame: During all day ]
      Modification in social interactions using movies of the study day and sociometric badges
    • Gait [ Time Frame: 2 hours after the administration ]
      Gait analysis using the Kinect camera
    • Approach-avoidance behavior [ Time Frame: 5 hours after the administration ]
      Whole-body approach-avoidance behavior to positive/negative stimuli
    • Face expression of sickness [ Time Frame: Before the administration and 2 and 7.5 hours after ]
      Face expression of sickness measured using photos of the subject with a neutral face expression
    • Change in skin color [ Time Frame: Before the administration and 1,2,3,4,5,7 hours after ]
      Change in skin color measurement using a spectrophotometer
    • Motivation as measured using the Effort Expenditure for Rewards Task (EEfRT) [ Time Frame: 4 hours after the administration ]
      Choices of hard task (vs easy task) in the EEfRT


    Original Secondary Outcome: Same as current

    Information By: Karolinska Institutet

    Dates:
    Date Received: April 29, 2015
    Date Started: February 2015
    Date Completion:
    Last Updated: August 19, 2015
    Last Verified: August 2015