Inflammation and Brain Function - Pilot Study

Study Overview
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Brief Summary
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In this randomized double blind cross-over study 8 healthy persons were injected with 0.8 ng/kg body weight lipopolysaccharide (LPS) /endotoxin and placebo at two different occasions. The aim was to investigate how pain sensitivity and health perception change in response to an acute immune activation.

Detailed Description
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Eight healthy participants were included in this randomized and balanced double blind cross-over study. They were injected two times, once with the active component and once with placebo. Participants were recruited by advertising and screened through questionnaires and a health examination by a physician. They were asked not to engage in strenuous physical activities, sleep regular hours and refrain from alcohol the day before the experiment. If the participants felt ill, e.g. coming down with a cold, they were instructed to call and were rescheduled for a later appointment. C-reactive protein (CRP) was assessed to exclude participants having an ongoing infection on the experimental day. Pregnancy was also an exclusion criteria and a pregnancy test was administered for all female participants on arrival. Several pain sensitivity measures were performed baseline and at peak inflammatory response 1-2 hours after injection. Subjects filled out questionnaires at baseline, 90 minutes and 4,5 hours after injection. The study and the procedures used in the study are described in detail here: https://openarchive.ki.se/xmlui/bitstream/handle/10616/44650/Thesis_Bianka_Karshikoff.pdf?sequence=8&isAllowed=y The following papers have been published using data from this study: Olsson MJ, Lundstrom JN, Kimball BA, Gordon AR, Karshikoff B, Hosseini N, Sorjonen K, Olgart Hoglund C, Solares C, Soop A, Axelsson J & Lekander M. The Scent of Disease: Human Body Odor Contains an Early Chemosensory Cue of Sickness. Psychol Sci. 2014 Jan 22. Sundelin T, Karshikoff B, Axelsson E, Hoglund CO, Lekander M, Axelsson J. Sick man walking: Perception of health status from body motion. Brain Behav Immun. 2015;48:53-6. Karshikoff B, Lekander M, Soop A, Lindstedt F, Ingvar M Kosek E, Olgart Höglund C, & Axelsson J. Modality and sex differences in pain sensitivity during human endotoxemia. Brain, Behavior, and Immunity. 2015 May;46:35-43

Official Title
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Inflammation Och hjärnfunktion - Pilotstudie

Conditions
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Sickness Behavior

Intervention / Treatment
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* Biological: Lipopolysaccharide
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy subjects Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

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: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Endotoxin<br>0.8 ng lipopolysaccharide/kg body weight injection | Biological: Lipopolysaccharide<br>* Endotoxin at 0.8 ng/kg of body weight administered intravenously (Escherichia Coli, Lot nr G3E0609, United States Pharmacopeia Rockville, MD)<br>* Other names: LPS;|
| Placebo Comparator: Placebo<br>Saline injection | Biological: Placebo<br>* Saline administered intravenously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in interoceptive vs exteroceptive focus | Rating of concordance of heartbeat vs signal and change in tone of signal | 7 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in self-rated health | Two questions were used to assess self-rated health 1how do you rate your general health status rated on a 5 grade Likert scale very good to very poor and 2how is your health right now rated on a 7 grade Likert scale from excellent to very poor | 7 hours | 
| Change in pain perception | Both deep and cutaneous pain at threshold and suprathreshold noxious levels. Heat- and cold (cutaneous) pain sensitivity was assessed for threshold stimuli and intense noxious stimuli, as well as pressure (deep) pain thresholds and CPM (descending pain inhibition). | 7 hours | 
| Change in facial apparence | Photos were taken under standardised conditions before and after injection | 2 hours | 
| Change in gait | The participants were filmed walking before and after injection | 2 h | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sickness behavior, Cytokines, Psychoneuroimmunology