Sickness BehaviorNCT03551184
Inflammation and Brain Function - Main Study
A study testing Endotoxin in people with Sickness Behavior, run by Karolinska Institutet.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 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
- 52 participants
- Where
- No sites listed yet
- Study dates
- Oct 2010to Mar 2011
- 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 55 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 11Show 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
- Known or risk of metal inserted in body
- Claustrophobic tendensies
About this study
Official title: Inflammation Och hjärnfunktion - Huvudstudie
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.
Read the 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
- Conditions
- Sickness Behavior
- Being tested
- Endotoxin, Placebo
- Keywords
- Sickness behavior, Endotoxin, Lipopolysaccharide, 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
Endotoxin at 0.6 ng/kg of body weight administered intravenously (Escherichia Coli, Lot nr G3E0609, United States Pharmacopeia Rockville, MD)
PlaceboBiological
Saline administered intravenously
| Study group | Role | What they receive |
|---|---|---|
| Endotoxin | Active comparator | Endotoxin 0.6 ng/kg body weight injection Receives: Biological: Endotoxin |
| Placebo | Placebo comparator | Saline injection Receives: Biological: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pain sensitivity (cutaneous and deep)
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).
Measured: 7.5 hours
Brain function
BOLD activity from MR scans
- Functional connectivity of the insular cortex during acute inflammation, in relation to symptoms of sickness.
- 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.
- Changes in brain function during an emotional task with an interoceptive component during acute inflammation.
Measured: 7.5 hours
Secondary outcomes (2)
Self-rated health
"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
Measured: 4.5 hours
Facial appearence
Photos were taken under standardised conditions before and after injection
Measured: 2 h
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2018
- Study startOct 2010
- Primary completionMar 2011
- Study completionMar 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Lead sponsor
- Karolinska Institutet
- Sponsor type
- University, hospital or other
- 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
- Responsible party
- Principal investigator, Mats Lekander, Karolinska Institutet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03551184
- Sponsor's protocol ID
- 2010/1363-32
- Status last verified
- May 2018
- First submitted
- 29 May 2018
- Last updated
- 11 Jun 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Inflammation Och hjärnfunktion - Huvudstudie
- ClinicalTrials.gov ID
- NCT03551184
- Acronym / sponsor ID
- 2010/1363-32
- Conditions
- Sickness Behavior
- Keywords
- Sickness behavior, Endotoxin, Lipopolysaccharide, Psychoneuroimmunology
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 52 participants (actual)
- Lead sponsor
- Karolinska InstitutetUniversity, hospital or other
- 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
- Study start
- Oct 2010 (actual)
- Primary completion
- Mar 2011 (actual)
- Study completion
- Mar 2011 (actual)
- First posted
- 11 Jun 2018 (actual)
- 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.
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
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Endotoxin | Active comparator | Biological: EndotoxinEndotoxin 0.6 ng/kg body weight injection |
| Placebo | Placebo comparator | Biological: PlaceboSaline injection |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Healthy subjects
Key exclusion criteria (11 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, LipopolysaccharideEndotoxin at 0.6 ng/kg of body weight administered intravenously (Escherichia Coli, Lot nr G3E0609, United States Pharmacopeia Rockville, MD) | Biological | Endotoxin |
| PlaceboSaline administered intravenously | Biological | Placebo |
Primary outcome
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).
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.
2 secondary outcomes
Self-rated health
Time frame: 4.5 hours
Facial appearence
Time frame: 2 h
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 11 Jun 2018.
- Individual participant dataSharing planned: Undecided
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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 11 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 11 Jun 2018. 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?
Pain sensitivity (cutaneous and deep) (time frame: 7.5 hours). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 11 Jun 2018.