Endotoxin-induced Inflammatory and Behavioral Responses and Predictors of Individual Differences

NCT02529592 | Completed

• 1 other identifier: LPS 2.0 - 2014/1946-31
• Study Type: interventional
• Target: 22
• Locations: 0 countries
• Sites: N/A

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 will be completed by participants just before the endotoxin or sodium chloride injection, three hours and 7.5 hours after the injection. A short questionnaire assessing sickness behavior (SicknessQ) will be repeatedly completed by participants from just before to 7.5 hours after the endotoxin or sodium chloride injection. Several behavioral tests will be used, including a motivation task, a test assessing behavioral response to negative and sickness stimuli. Analysis of gait and motion, as well as of social interactions, will be performed. Photographs will be taken for the further rating of the faces.

Conditions

Sickness Behavior

Keywords

Sickness behavior; Cytokines; Psychoneuroimmunology

Outcome Measures

Primary Outcomes (19)

• Change from baseline in sickness behavior as measured using the sicknessQ

  Change in sickness behavior evaluated using the self-assessment questionnaire sicknessQ

  Before the administration and 1.5, 3, 5 and 7 hours after the administration

• Change from baseline in anxiety state as measured using the STAI-State

  Change in symptoms of anxiety evaluated using the self-assessment questionnaire State part of the State-Trait Anxiety Inventory (STAI)

  Before the administration and 3 and 7 hours after the administration

• Change from baseline in psychological state as measured using the SCAS

  Change in mood alterations evaluated using the self-assessment questionnaire Swedish Core Affect Scales (SCAS)

  Before the administration and 3 and 7 hours after the administration

• Change from baseline in pain as measured using the short McGill questionnaire

  Change in symptoms of pain evaluated using the self-assessment questionnaire Mc Gill questionnaire - short version

  Before the administration and 3 and 7 hours after the administration

• Change from baseline in sleepiness as measured using the KSS

  Change in sleepiness evaluated using the Karolinska Sleepiness Scale (KSS)

  Before the administration and 3 and 7 hours after the administration

• Change from baseline in systemic IL-6 concentrations

  Change in plasma concentration of the pro-inflammatory cytokine interleukin-6 (IL-6)

  Before the administration and 1, 1.5, 2, 3, 4, 5, 7 hours after the administration

• Change from baseline in systemic TNF-a concentrations

  Change in plasma concentration of the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-a)

  Before the administration and 1, 1.5, 2, 3, 4, 5, 7 hours after the administration

• Change from baseline in systemic IL-8 concentrations

  Change in plasma concentration of the pro-inflammatory cytokine interleukin-8 (IL-8)

  Before the administration and 1, 1.5, 2, 3, 4, 5, 7 hours after the administration

• Change from baseline in systemic HMGB1 concentrations

  Change in plasma concentration of the pro-inflammatory cytokine high-mobility group box 1 (HMGB1)

  Before the administration and 1, 1.5, 2, 3, 4, 5, 7 hours after the administration

• Change from baseline in systemic IL-1B concentrations

  Change in plasma concentration of the pro-inflammatory cytokine interleukin-1 beta (IL-1B)

  Before the administration and 1, 1.5, 2, 3, 4, 5, 7 hours after the administration

• Change from baseline in systemic IL-10 concentrations

  Change in plasma concentration of the anti-inflammatory cytokine interleukin-10 (IL-10)

  Before the administration and 1, 1.5, 2, 3, 4, 5, 7 hours after the administration

• Change from baseline in systemic IL-1ra concentrations

  Change in plasma concentration of the anti-inflammatory cytokine interleukin-1 receptor antagonist (IL-1ra)

  Before the administration and 1, 1.5, 2, 3, 4, 5, 7 hours after the administration

• Change from baseline in heart rate

  Change in heart rate assessed using a cardiac monitoring

  Before the administration and every half hour up to 7.5 hours after the administration

• Change from baseline in systolic blood pressure

  Change in systolic blood pressure assessed using a cardiac monitoring

  Before the administration and every half hour up to 7.5 hours after the administration

• Change from baseline in diastolic blood pressure

  Change in diastolic blood pressure assessed using a cardiac monitoring

  Before the administration and every half hour up to 7.5 hours after the administration

• Change from baseline in body temperature

  Change in body temperature measured using an ear thermometer

  Before the administration and every half hour up to 7.5 hours after the administration

• Change from baseline in headache scores as measured using a numerical scale

  Change in headache scores measured using a numerical scale ranging from 0 (no headache) to 10 (most unbearable headache)

  Before the administration and every half hour up to 7.5 hours after the administration

• Change from baseline in nausea scores as measured using a numerical scale

  Change in nausea scores measured using a numerical scale ranging from 0 (no nausea) to 10 (most unbearable nausea)

  Before the administration and every half hour up to 7.5 hours after the administration

• Change from baseline in back pain scores as measured using a numerical scale

  Change in back pain scores measured using a numerical scale ranging from 0 (no back pain) to 10 (most unbearable back pain)

  Before the administration and every half hour up to 7.5 hours after the administration

Secondary Outcomes (10)

• Change in cell expression of blood microparticles

  Before the administration and 1, 1.5, 2, 3, 4, 5, 7 hours after the administration

• Modification in genetic markers

  Before the administration and 1, 2, 4, 7 hours after the administration

• Change in expression of immune cell markers

  Before the administration and 1, 2, 3, 4, 7 hours after the administration

• Change in odor compounds

  Before and after the administration

• Changes in social interaction

  During all day

Study Arms (2)

Endotoxin

EXPERIMENTAL

Endotoxin at 2ng/kg of body weight administered intravenously

Biological: Endotoxin

Placebo

PLACEBO COMPARATOR

Placebo administered intravenously

Biological: Placebo

Interventions

Endotoxin BIOLOGICAL

Also known as: LPS, lipopolysaccharide

Endotoxin

Placebo BIOLOGICAL

Also known as: NaCl 0.9%, saline

Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy subjects

You may not qualify if:

• Diagnosed physiological or psychiatric disease
• Needle anxiety or blood phobia
• Regular medication (excluding contraceptive pill)
• Infection in the last two weeks
• Pregnancy or breastfeeding
• Smoking
• Excessive alcohol use
• Body mass index in the range of obesity (\>30 kg/m2) or underweight (\<18.5 kg/m2)
• Invisible veins in the antecubital area of the arms

Sponsors & Collaborators

• Karolinska Institutet: lead
• Danderyd Hospital: collaborator

Related Publications (2)

• Lasselin J, Petrovic P, Olsson MJ, Paues Goranson S, Lekander M, Jensen KB, Axelsson J. Sickness behavior is not all about the immune response: Possible roles of expectations and prediction errors in the worry of being sick. Brain Behav Immun. 2018 Nov;74:213-221. doi: 10.1016/j.bbi.2018.09.008. Epub 2018 Sep 11.

  PMID: 30217536 DERIVED

• Axelsson J, Sundelin T, Olsson MJ, Sorjonen K, Axelsson C, Lasselin J, Lekander M. Identification of acutely sick people and facial cues of sickness. Proc Biol Sci. 2018 Jan 10;285(1870):20172430. doi: 10.1098/rspb.2017.2430.

  PMID: 29298938 DERIVED

MeSH Terms

Conditions

Illness Behavior

Interventions

Endotoxins; Lipopolysaccharides; Sodium Chloride

Condition Hierarchy (Ancestors)

Behavior

Intervention Hierarchy (Ancestors)

Bacterial Toxins; Toxins, Biological; Biological Factors; Glycoconjugates; Carbohydrates; Polysaccharides, Bacterial; Polysaccharides; Lipids; Antigens, Bacterial; Antigens; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 29, 2015
• First Posted: August 20, 2015
• Study Start: February 1, 2015
• Primary Completion: April 1, 2015
• Study Completion: April 1, 2015
• Last Updated: August 20, 2015

Record last verified: 2015-08