Sickness BehaviorNCT02529592
Endotoxin-induced Inflammatory and Behavioral Responses and Predictors of Individual Differences
A study testing Endotoxin in people with Sickness Behavior, run by Karolinska Institutet.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Sickness Behavior
- What is being tested?
- Endotoxin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 22 participants
- Where
- No sites listed yet
- Study dates
- Feb 2015to Apr 2015
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy subjects
Who cannot join
- 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
Show all 9Show fewer
- 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
About this study
Official title: Endotoxin-induced Inflammatory and Behavioral Responses and Predictors of Individual Differences: A Randomized, Double-blind Placebo Controlled Study on Healthy Human Volunteers
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.
Read more
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.
Read the detailed description
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:
- Trial 1: endotoxin. Subjects will receive an intravenous injection of endotoxin at 2 ng/kg of body weight.
- 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 mixed with 5 milliliter (mL) of sterile water.
Study procedure
The study will be conducted at Department of Clinical Sciences, Danderyd Hospital.
Prior to inclusion and randomization, subjects will come at the hospital in order to be subjected to a medical examination, including an electrocardiogram and blood laboratory analyses. Socio-demographic data and medical history will be assessed at this occasion, as well as body variables (weight, height, body composition) and physical activity using the Swedish version of the IPAQ (International Physical Activity Questionnaire). History of major depression will be assessed using the Mini-International Neuropsychiatric Interview (M.I.N.I.) for major depression. Psychological variables that could affect the behavioral (or immune) response to LPS, and which are not believed to change between the screening day and the trial days, will be also assessed at that time, using several web-based self-assessment questionnaires. These measures will include the subjects' perception of the body and health risk (e.g., interoceptive awareness, perceived vulnerability to disease, health anxiety and disgust reactivity, somatosensory amplification, fear of anxiety-related sensations) and psychological well-being (e.g., perceived stress, optimism, social support, cognitive well-being). The overall time for the medical examination will be of 30-45 minutes. The time to complete questionnaires is estimated to approximately 45 minutes but can be done from home. The participants will also receive a kit with a T-shirt (with sewn-in cotton pads) and a scent-free soap. Participants will be asked to wear the T-shirt in the morning (after washing armpits) on each trial day, and take it off after their arrival. This will allow collecting pre-treatment (baseline) samples of body odor.
Participants will then be subjected to the two trials performed in a randomized order, with at least six weeks of wash-out: endotoxin versus placebo.
The participants will be asked to restrain from strenuous exercise and alcohol taking 48 hours before the trial day, to avoid strong spices 24 hours before the trial day, and to take a light breakfast the morning of the trial day. Participants will arrive on the morning (at 7.30AM). They will turn in their morning T-shirt (see above) and change to a new T-shirt (with sewn-in cotton pads in the armpit) to wear during all day. The T-shirts will be used for behavioral assessment and analysis of body odor compound. Shortly after their arrival, two intravenous catheters will be placed: one for blood sampling at one arm and one at one hand for the injection of endotoxin or sodium chloride that will be removed after the injection. An anesthetic cream will be provided to spread on their arm in order to minimize the pain of venipuncture. Subjects will then rest for at least 30 minutes.
Injection of endotoxin or sodium chloride will be performed when the rest is completed (around 8.30AM). Blood samples (10 mL in EDTA (Ethylenediaminetetraacetic acid) tubes and 10 mL in sodium citrate tubes) 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. In addition, 2.5 mL in PAXGene™ tubes will be taken before and 2, 4 and 7.5 hours after the injection. Two additional samples in EDTA tubes (8 mL of blood) will be taken before the injection and 3 and 7.5 hours after the injection. The total quantity of blood taken will be of about 200 mL, corresponding to a third of the amount given at a blood donation. Blood samples will be used to measure concentrations of pro- and anti-inflammatory cytokines and other inflammatory markers (e.g., C-Reactive protein - CRP) using Enzyme-Linked Immunosorbent Assay (ELISA), immune cell subpopulations and concentrations of microparticles using flow cytometry, genetic markers using Cap analysis gene expression (CAGE) analyses and white blood cell count and differential.
Urine samples will be taken before the endotoxin or sodium chloride injection (i.e., before the catheters are placed) and as late as possible after the injection (classically around four hours after the injection).
Participants will be monitored with continuous electrocardiogram. Oxygen saturation (SO2), blood pressure and body temperature will be monitored every 30 minutes. Nitrogen dioxide (NO2) will be monitored continuously, methemoglobin checked at the same time than each blood sample.
Self-assessment questionnaires assessing behavioral and psychological variables will be completed by participants just before the endotoxin or sodium chloride injection (during the rest period), 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. Subjects will be filmed when in bed and will wear a sociometric badge, in order to analyze participants' behavioral response to a standardized situation of social interaction.
Photographs will be taken before (i.e., before the catheters are placed), two hours after and 7.5 hours after the injection, for the further rating of the faces (e.g., health, attractiveness, tiredness). In parallel, skin color will be measured at the same time than blood samples (except T1.5) in order to assess a potential mediating effect of faces' health ratings. Analysis of subjects' gait and motion will be performed two and half hours after the injection. Short computerized cognitive tests will be performed after these tests, just before three hours after the injection. Subjects will perform a motivation task after completing the questionnaires three hours after the injection. In addition, two tests assessing behavior in response to positive/negative and healthy/sickness stimuli (an approach-avoidance behavior test and a regulation of emotion test) will be executed three hours and half after the injection.
Participants will be allowed to take a light meal (snack and juice drink) around lunch time (12.30) and will hand in their T-shirt just before five and half hours after the injection.
The last blood samples will be taken 7.5 hours after the injection and participants will be discharged.
Monitoring of the experiment will be done by a medical doctor, supervised by a specialist in anesthesia and intensive care.
- Conditions
- Sickness Behavior
- Being tested
- Endotoxin, Placebo
- Keywords
- Sickness behavior, Cytokines, Psychoneuroimmunology
- Medical subject headings
- Illness Behavior
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EndotoxinBiological
Also called LPS, lipopolysaccharide
PlaceboBiological
Also called NaCl 0.9%, saline
| Study group | Role | What they receive |
|---|---|---|
| Endotoxin | Experimental | Endotoxin at 2ng/kg of body weight administered intravenously Receives: Biological: Endotoxin |
| Placebo | Placebo comparator | Placebo administered intravenously Receives: Biological: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in sickness behavior as measured using the sicknessQ
Change in sickness behavior evaluated using the self-assessment questionnaire sicknessQ
Measured: 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)
Measured: 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)
Measured: 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
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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
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).
Measured: Before the administration and 1, 1.5, 2, 3, 4, 5, 7 hours after the administration
Modification in genetic markers
Modification in genetic markers measured using CAGE analysis from PAXGene blood samples
Measured: Before the administration and 1, 2, 4, 7 hours after the administration
Change in expression of immune cell markers
Change in expression of immune cell subpopulations markers using flow cytometry from frozen whole blood in 10% Dimethylsulfoxid (DMSO)
Measured: Before the administration and 1, 2, 3, 4, 7 hours after the administration
Change in odor compounds
Change in abundance of volatile odor compounds analyzed using gas chromatography mass spectrometry (GC-MS) from tee-shirt samples and urine samples
Measured: Before and after the administration
Changes in social interaction
Modification in social interactions using movies of the study day and sociometric badges
Measured: During all day
Gait
Gait analysis using the Kinect camera
Measured: 2 hours after the administration
Approach-avoidance behavior
Whole-body approach-avoidance behavior to positive/negative stimuli
Measured: 5 hours after the administration
Face expression of sickness
Face expression of sickness measured using photos of the subject with a neutral face expression
Measured: Before the administration and 2 and 7.5 hours after
Change in skin color
Change in skin color measurement using a spectrophotometer
Measured: Before the administration and 1,2,3,4,5,7 hours after
Motivation as measured using the Effort Expenditure for Rewards Task (EEfRT)
Choices of hard task (vs easy task) in the EEfRT
Measured: 4 hours after the administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Aug 2015 (estimated)
- Study startFeb 2015
- Primary completionApr 2015
- Study completionApr 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Sickness BehaviorStudies of the same condition, open and under way.
- More trials run by Karolinska InstitutetThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Karolinska Institutet
- Sponsor type
- University, hospital or other
- Collaborators
- Danderyd Hospital
- Responsible party
- Principal investigator, Mats Lekander, Karolinska Institutet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02529592
- Sponsor's protocol ID
- LPS 2.0 - 2014/1946-31
- Status last verified
- Aug 2015
- First submitted
- 29 Apr 2015
- Last updated
- 20 Aug 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 30217536Axelsson 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.
PubMed 29298938
Study at a glance
From the registry record, last updated by the sponsor on 20 Aug 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Endotoxin-induced Inflammatory and Behavioral Responses and Predictors of Individual Differences: A Randomized, Double-blind Placebo Controlled Study on Healthy Human Volunteers
- ClinicalTrials.gov ID
- NCT02529592
- Acronym / sponsor ID
- LPS 2.0 - 2014/1946-31
- Conditions
- Sickness Behavior
- Keywords
- Sickness behavior, Cytokines, Psychoneuroimmunology
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Karolinska InstitutetUniversity, hospital or other
- Collaborators
- Danderyd Hospital
- Study start
- Feb 2015
- Primary completion
- Apr 2015 (actual)
- Study completion
- Apr 2015 (actual)
- First posted
- 20 Aug 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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:
- Trial 1: endotoxin. Subjects will receive an intravenous injection of endotoxin at 2 ng/kg of body weight.
- 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 mixed with 5 milliliter (mL) of sterile water.
Study procedure
The study will be conducted at Department of Clinical Sciences, Danderyd Hospital.
Prior to inclusion and randomization, subjects will come at the hospital in order to be subjected to a medical examination, including an electrocardiogram and blood laboratory analyses. Socio-demographic data and medical history will be assessed at this occasion, as well as body variables (weight, height, body composition) and physical activity using the Swedish version of the IPAQ (International Physical Activity Questionnaire). History of major depression will be assessed using the Mini-International Neuropsychiatric Interview (M.I.N.I.) for major depression. Psychological variables that could affect the behavioral (or immune) response to LPS, and which are not believed to change between the screening day and the trial days, will be also assessed at that time, using several web-based self-assessment questionnaires. These measures will include the subjects' perception of the body and health risk (e.g., interoceptive awareness, perceived vulnerability to disease, health anxiety and disgust reactivity, somatosensory amplification, fear of anxiety-related sensations) and psychological well-being (e.g., perceived stress, optimism, social support, cognitive well-being). The overall time for the medical examination will be of 30-45 minutes. The time to complete questionnaires is estimated to approximately 45 minutes but can be done from home. The participants will also receive a kit with a T-shirt (with sewn-in cotton pads) and a scent-free soap. Participants will be asked to wear the T-shirt in the morning (after washing armpits) on each trial day, and take it off after their arrival. This will allow collecting pre-treatment (baseline) samples of body odor.
Participants will then be subjected to the two trials performed in a randomized order, with at least six weeks of wash-out: endotoxin versus placebo.
The participants will be asked to restrain from strenuous exercise and alcohol taking 48 hours before the trial day, to avoid strong spices 24 hours before the trial day, and to take a light breakfast the morning of the trial day. Participants will arrive on the morning (at 7.30AM). They will turn in their morning T-shirt (see above) and change to a new T-shirt (with sewn-in cotton pads in the armpit) to wear during all day. The T-shirts will be used for behavioral assessment and analysis of body odor compound. Shortly after their arrival, two intravenous catheters will be placed: one for blood sampling at one arm and one at one hand for the injection of endotoxin or sodium chloride that will be removed after the injection. An anesthetic cream will be provided to spread on their arm in order to minimize the pain of venipuncture. Subjects will then rest for at least 30 minutes.
Injection of endotoxin or sodium chloride will be performed when the rest is completed (around 8.30AM). Blood samples (10 mL in EDTA (Ethylenediaminetetraacetic acid) tubes and 10 mL in sodium citrate tubes) 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. In addition, 2.5 mL in PAXGene™ tubes will be taken before and 2, 4 and 7.5 hours after the injection. Two additional samples in EDTA tubes (8 mL of blood) will be taken before the injection and 3 and 7.5 hours after the injection. The total quantity of blood taken will be of about 200 mL, corresponding to a third of the amount given at a blood donation. Blood samples will be used to measure concentrations of pro- and anti-inflammatory cytokines and other inflammatory markers (e.g., C-Reactive protein - CRP) using Enzyme-Linked Immunosorbent Assay (ELISA), immune cell subpopulations and concentrations of microparticles using flow cytometry, genetic markers using Cap analysis gene expression (CAGE) analyses and white blood cell count and differential.
Urine samples will be taken before the endotoxin or sodium chloride injection (i.e., before the catheters are placed) and as late as possible after the injection (classically around four hours after the injection).
Participants will be monitored with continuous electrocardiogram. Oxygen saturation (SO2), blood pressure and body temperature will be monitored every 30 minutes. Nitrogen dioxide (NO2) will be monitored continuously, methemoglobin checked at the same time than each blood sample.
Self-assessment questionnaires assessing behavioral and psychological variables will be completed by participants just before the endotoxin or sodium chloride injection (during the rest period), 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. Subjects will be filmed when in bed and will wear a sociometric badge, in order to analyze participants' behavioral response to a standardized situation of social interaction.
Photographs will be taken before (i.e., before the catheters are placed), two hours after and 7.5 hours after the injection, for the further rating of the faces (e.g., health, attractiveness, tiredness). In parallel, skin color will be measured at the same time than blood samples (except T1.5) in order to assess a potential mediating effect of faces' health ratings. Analysis of subjects' gait and motion will be performed two and half hours after the injection. Short computerized cognitive tests will be performed after these tests, just before three hours after the injection. Subjects will perform a motivation task after completing the questionnaires three hours after the injection. In addition, two tests assessing behavior in response to positive/negative and healthy/sickness stimuli (an approach-avoidance behavior test and a regulation of emotion test) will be executed three hours and half after the injection.
Participants will be allowed to take a light meal (snack and juice drink) around lunch time (12.30) and will hand in their T-shirt just before five and half hours after the injection.
The last blood samples will be taken 7.5 hours after the injection and participants will be discharged.
Monitoring of the experiment will be done by a medical doctor, supervised by a specialist in anesthesia and intensive care.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Endotoxin | Experimental | Biological: EndotoxinEndotoxin at 2ng/kg of body weight administered intravenously |
| Placebo | Placebo comparator | Biological: PlaceboPlacebo administered intravenously |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Healthy subjects
Key exclusion criteria (9 listed)
- Diagnosed physiological or psychiatric disease
- Needle anxiety or blood phobia
- Regular medication (excluding contraceptive pill)
- Infection in the last two weeks
- Pregnancy or breastfeeding
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EndotoxinAlso: LPS, lipopolysaccharide | Biological | Endotoxin |
| PlaceboAlso: NaCl 0.9%, saline | Biological | Placebo |
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 administration and 1, 1.5, 2, 3, 4, 5, 7 hours after the administration
Change in plasma concentration of the pro-inflammatory cytokine interleukin-6 (IL-6)
Change from baseline in systemic TNF-a concentrations
Time frame: Before the administration and 1, 1.5, 2, 3, 4, 5, 7 hours after the administration
Change in plasma concentration of the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-a)
Change from baseline in systemic IL-8 concentrations
Time frame: Before the administration and 1, 1.5, 2, 3, 4, 5, 7 hours after the administration
Change in plasma concentration of the pro-inflammatory cytokine interleukin-8 (IL-8)
Change from baseline in systemic HMGB1 concentrations
Time frame: Before the administration and 1, 1.5, 2, 3, 4, 5, 7 hours after the administration
Change in plasma concentration of the pro-inflammatory cytokine high-mobility group box 1 (HMGB1)
Change from baseline in systemic IL-1B concentrations
Time frame: Before the administration and 1, 1.5, 2, 3, 4, 5, 7 hours after the administration
Change in plasma concentration of the pro-inflammatory cytokine interleukin-1 beta (IL-1B)
Change from baseline in systemic IL-10 concentrations
Time frame: Before the administration and 1, 1.5, 2, 3, 4, 5, 7 hours after the administration
Change in plasma concentration of the anti-inflammatory cytokine interleukin-10 (IL-10)
Change from baseline in systemic IL-1ra concentrations
Time frame: Before the administration and 1, 1.5, 2, 3, 4, 5, 7 hours after the administration
Change in plasma concentration of the anti-inflammatory cytokine interleukin-1 receptor antagonist (IL-1ra)
Change from baseline in heart rate
Time frame: Before the administration and every half hour up to 7.5 hours after the administration
Change in heart rate assessed using a cardiac monitoring
Change from baseline in systolic blood pressure
Time frame: Before the administration and every half hour up to 7.5 hours after the administration
Change in systolic blood pressure assessed using a cardiac monitoring
Change from baseline in diastolic blood pressure
Time frame: Before the administration and every half hour up to 7.5 hours after the administration
Change in diastolic blood pressure assessed using a cardiac monitoring
Change from baseline in body temperature
Time frame: Before the administration and every half hour up to 7.5 hours after the administration
Change in body temperature measured using an ear thermometer
Change from baseline in headache scores as measured using a numerical scale
Time frame: Before the administration and every half hour up to 7.5 hours after the administration
Change in headache scores measured using a numerical scale ranging from 0 (no headache) to 10 (most unbearable headache)
Change from baseline in nausea scores as measured using a numerical scale
Time frame: Before the administration and every half hour up to 7.5 hours after the administration
Change in nausea scores measured using a numerical scale ranging from 0 (no nausea) to 10 (most unbearable nausea)
Change from baseline in back pain scores as measured using a numerical scale
Time frame: Before the administration and every half hour up to 7.5 hours after the administration
Change in back pain scores measured using a numerical scale ranging from 0 (no back pain) to 10 (most unbearable back pain)
10 secondary outcomes
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
Modification in genetic markers
Time frame: Before the administration and 1, 2, 4, 7 hours after the administration
Change in expression of immune cell markers
Time frame: Before the administration and 1, 2, 3, 4, 7 hours after the administration
Change in odor compounds
Time frame: Before and after the administration
Changes in social interaction
Time frame: During all day
Gait
Time frame: 2 hours after the administration
Approach-avoidance behavior
Time frame: 5 hours after the administration
Face expression of sickness
Time frame: Before the administration and 2 and 7.5 hours after
Change in skin color
Time frame: Before the administration and 1,2,3,4,5,7 hours after
Motivation as measured using the Effort Expenditure for Rewards Task (EEfRT)
Time frame: 4 hours after the administration
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Aug 2015.
- Derived from this study: PubMed 30217536Lasselin 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.
- Derived from this study: PubMed 29298938Axelsson 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A study testing Endotoxin in people with Sickness Behavior, run by Karolinska Institutet.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Aug 2015. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 19 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02529592, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Aug 2015.