Clinical trial NCT03551184: Inflammation and Brain Function - Main Study
Official title: Inflammation Och hjärnfunktion - Huvudstudie
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Sickness Behavior
Keywords: Sickness behavior
Endotoxin
Lipopolysaccharide
Psychoneuroimmunology
Lead sponsor: Karolinska Institutet
Sponsor class: OTHER
Collaborators: name: University of California, San Francisco
name: The Swedish Society of Medicine
name: Swedish Heart Lung Foundation
name: The Swedish Research Council
name: Swedish Council for Working Life and Social Research
name: Stockholm University
First posted: 2018-06-11
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: In this randomized double blind study, 52 healthy participants were injected with either 0.6 ng/kg body weight or placebo to test if changes in pain sensitivity is associated with change in neural activity using BOLD MR scanning.

Detailed description: 52 healthy participants were included in this randomized double blind study. Participants were injected once, and randomized to injection with with the active component or 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. Pain sensitivity measures were tested at baseline and at peak inflammatory response 1-2 hours after injection. Both deep and cutaneous pain at threshold and suprathreshold noxious levels were tested. 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). These tests were conducted while the participants were in the MR-scanner to investigate neural correlates to change in pain sensitivity. Subjects filled out questionnaires at baseline, 90 minutes, 3.5 and 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 using data from this study is published:

Lindstedt F, Karshikoff B, Schalling M, Olgart Hoglund C, Ingvar M, Lekander M \& Kosek E. Serotonin-1A Receptor Polymorphism (rs6295) Associated with Thermal Pain Perception. PLOS ONE. 2012;7(8):e43221. Epub 2012/09/07.

Karshikoff B, Jensen KB, Kosek E, Kalpouzos G, Soop A, Ingvar M, Olgart Höglund C, Lekander M, Axelsson J. Why sickness hurts: A central mechanism for pain induced by peripheral inflammation. Brain, Behavior, and Immunity 2016 Oct;57:38-46.

Lekander M, Karshikoff B, Johansson E, Soop A, Fransson P, Lundström J N, Andreasson A, Ingvar M, Petrovic P, Axelsson J/Nilsonne G. Intrinsic functional connectivity of insular cortex and symptoms of sickness during acute experimental inflammation. Brain, Behavior, and Immunity 2016 Aug;56:34-41.

Andreasson A, Wicksell RK, Lodin K, Karshikoff B, Axelsson J, Lekander M. A Global Measure of Sickness Behavior: Development of the Sickness Questionnaire (SicknessQ). Journal of Health Psychology. 2016 Jul 24.

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

Eligibility criteria: 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
* Known or risk of metal inserted in body
* Claustrophobic tendensies

Primary outcomes:
measure: Pain sensitivity (cutaneous and deep)
timeFrame: 7.5 hours
measure: Brain function
timeFrame: 7.5 hours
Secondary outcomes:
measure: Self-rated health
timeFrame: 4.5 hours
measure: Facial appearence
timeFrame: 2 h
Other outcomes:
Locations:
Study officials:
References: