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Inflammation and Brain Function - Main Study

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ClinicalTrials.gov Identifier: NCT03551184
Recruitment Status : Completed
First Posted : June 11, 2018
Last Update Posted : June 11, 2018
Sponsor:
Collaborators:
University of California, San Francisco
The Swedish Society of Medicine
Swedish Heart Lung Foundation
The Swedish Research Council
Swedish Council for Working Life and Social Research
Stockholm University
Information provided by (Responsible Party):
Mats Lekander, Karolinska Institutet

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.

Condition or disease Intervention/treatment Phase
Sickness Behavior Biological: Endotoxin Biological: Placebo Not Applicable

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 52 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Basic Science
Official Title: Inflammation Och hjärnfunktion - Huvudstudie
Actual Study Start Date : October 2010
Actual Primary Completion Date : March 2011
Actual Study Completion Date : March 2011

Arm Intervention/treatment
Active Comparator: Endotoxin
Endotoxin 0.6 ng/kg body weight injection
Biological: Endotoxin
Endotoxin at 0.6 ng/kg of body weight administered intravenously (Escherichia Coli, Lot nr G3E0609, United States Pharmacopeia Rockville, MD)
Other Names:
  • LPS
  • Lipopolysaccharide

Placebo Comparator: Placebo
Saline injection
Biological: Placebo
Saline administered intravenously




Primary Outcome Measures :
  1. Pain sensitivity (cutaneous and deep) [ Time Frame: 7.5 hours ]
    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).

  2. Brain function [ Time Frame: 7.5 hours ]

    BOLD activity from MR scans

    1. Functional connectivity of the insular cortex during acute inflammation, in relation to symptoms of sickness.
    2. Changes in central pain mechanism during acute inflammation, assessed as activity in the insula and areas of the descending pain inhibitory pathways in the brain.
    3. Changes in brain function during an emotional task with an interoceptive component during acute inflammation.


Secondary Outcome Measures :
  1. Self-rated health [ Time Frame: 4.5 hours ]

    "How is your health right now?" rated on a 7 point Likert scale at baseline, after 90 minutes and after 4.5 hours.

    "How do you rate your general state of health?" rated on a 5-point Likert scale at 90 minutes post-injection


  2. Facial appearence [ Time Frame: 2 h ]
    Photos were taken under standardised conditions before and after injection



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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
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Responsible Party: Mats Lekander, Professor, Karolinska Institutet
ClinicalTrials.gov Identifier: NCT03551184    
Other Study ID Numbers: 2010/1363-32
First Posted: June 11, 2018    Key Record Dates
Last Update Posted: June 11, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Mats Lekander, Karolinska Institutet:
Sickness behavior
Endotoxin
Lipopolysaccharide
Psychoneuroimmunology
Additional relevant MeSH terms:
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Inflammation
Illness Behavior
Pathologic Processes