Inflammation and Brain Function - Pilot Study

Inflammation Och hjärnfunktion - Pilotstudie

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.

Study Overview

• Status: Completed
• Conditions: Sickness Behavior
• Intervention / Treatment: Biological: Lipopolysaccharide; Biological: Placebo

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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 1"how do you rate your general health status" rated on a 5 grade Likert scale very good to very poor and 2"how 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

Collaborators and Investigators

• Sponsor: Karolinska Institutet
• Collaborators: The Swedish Research Council; University of California, San Francisco; Swedish Council for Working Life and Social Research; Swedish Heart Lung Foundation; The Swedish Society of Medicine; Stockholm University

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2009
• Primary Completion (Actual): December 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: May 29, 2018
• First Submitted That Met QC Criteria: May 29, 2018
• First Posted (Actual): June 11, 2018

Study Record Updates

• Last Update Posted (Actual): June 11, 2018
• Last Update Submitted That Met QC Criteria: May 29, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: Cytokines; Psychoneuroimmunology; Sickness behavior
• Additional Relevant MeSH Terms: Pathologic Processes; Inflammation; Illness Behavior
• Other Study ID Numbers: 2008/955-31

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No