Endotoxin-induced Inflammatory and Behavioral Responses and Predictors of Individual Differences: A Randomized, Double-blind Placebo Controlled Study on Healthy Human Volunteers
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 22
- 主要终点
- Change from baseline in pain as measured using the short McGill questionnaire
研究概览
简要总结
The objective of the present study is to specifically assess the effect of lipopolysaccharide (LPS) administration on the development of behavioral symptoms and the underlying contribution of inflammatory processes. In particular, the investigators will assess the development of subjective and objective behavioral symptoms. In addition, the investigators will determine whether some psychological trait or state can predict and/or modulate the LPS-induced inflammatory and behavioral responses.
Twenty-five healthy subjects will be included. A placebo-controlled, double-blinded and cross-over design will be used. Subjects will receive an intravenous injection of endotoxin at 2 nanogram/kilogram (ng/kg) of body weight and an intravenous injection of sodium chloride as placebo of endotoxin injection at two different occasions.
Prior to inclusion and randomization, subjects will come at the hospital and will receive a medical examination. Psychological variables that could affect the behavioral (or immune) response to LPS will be assessed at that time, using several self-assessment questionnaires.
On the trial days, injection of endotoxin or sodium chloride will be performed and blood samples will be taken just before the endotoxin or sodium chloride injection and 1, 1.5, 2, 3, 4, 5, 6 and 7.5 hours after the injection. Blood samples will be used to measure several inflammatory and immune markers. Urine samples will be taken before the endotoxin or sodium chloride injection and as late as possible after the injection. Subjects will wear T-shirt all day. Urine and T-shirt samples will be used for behavioral assessment and analysis of body odor compound.
Self-assessment questionnaires assessing behavioral and psychological variables will be completed by participants just before the endotoxin or sodium chloride injection, three hours and 7.5 hours after the injection. A short questionnaire assessing sickness behavior (SicknessQ) will be repeatedly completed by participants from just before to 7.5 hours after the endotoxin or sodium chloride injection.
Several behavioral tests will be used, including a motivation task, a test assessing behavioral response to negative and sickness stimuli. Analysis of gait and motion, as well as of social interactions, will be performed. Photographs will be taken for the further rating of the faces.
详细描述
Study design
Twenty-five subjects will be included in the present study, which will follow a prospective, placebo-controlled and cross-over design. Participants will be blinded, as well as research personnel in charge of the participants and the laboratory.
Subjects will be randomly assigned in the cross-over design with two trials, with about four weeks wash-out between LPS stimulations:
- Trial 1: endotoxin. Subjects will receive an intravenous injection of endotoxin at 2 ng/kg of body weight.
- Trial 2: placebo. Subjects will receive an intravenous injection of sodium chloride as placebo of endotoxin injection.
Ten other healthy volunteers will be recruited in a pilot study prior the beginning of the main study, in order to test the behavioral tasks that will be used. These subjects will be recruited among the university staff or among university students. They will perform four specific behavioral tasks and will complete the questionnaires assessing psychological and behavioral variables in order to associate outcomes from the behavioral tasks to psychological and subjective behavioral assessments. No biological samples (blood, urine or tee-shirt samples) will be taken in subjects recruited in the pilot study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy subjects
排除标准
- •Diagnosed physiological or psychiatric disease
- •Needle anxiety or blood phobia
- •Regular medication (excluding contraceptive pill)
- •Infection in the last two weeks
- •Pregnancy or breastfeeding
- •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
结局指标
主要结局
Change from baseline in pain as measured using the short McGill questionnaire
时间窗: Before the administration and 3 and 7 hours after the administration
Change in symptoms of pain evaluated using the self-assessment questionnaire Mc Gill questionnaire - short version
Change from baseline in systemic TNF-a concentrations
时间窗: Before the administration and 1, 1.5, 2, 3, 4, 5, 7 hours after the administration
Change in plasma concentration of the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-a)
Change from baseline in systolic blood pressure
时间窗: Before the administration and every half hour up to 7.5 hours after the administration
Change in systolic blood pressure assessed using a cardiac monitoring
Change from baseline in body temperature
时间窗: Before the administration and every half hour up to 7.5 hours after the administration
Change in body temperature measured using an ear thermometer
Change from baseline in nausea scores as measured using a numerical scale
时间窗: Before the administration and every half hour up to 7.5 hours after the administration
Change in nausea scores measured using a numerical scale ranging from 0 (no nausea) to 10 (most unbearable nausea)
Change from baseline in systemic HMGB1 concentrations
时间窗: Before the administration and 1, 1.5, 2, 3, 4, 5, 7 hours after the administration
Change in plasma concentration of the pro-inflammatory cytokine high-mobility group box 1 (HMGB1)
Change from baseline in systemic IL-1ra concentrations
时间窗: Before the administration and 1, 1.5, 2, 3, 4, 5, 7 hours after the administration
Change in plasma concentration of the anti-inflammatory cytokine interleukin-1 receptor antagonist (IL-1ra)
Change from baseline in anxiety state as measured using the STAI-State
时间窗: Before the administration and 3 and 7 hours after the administration
Change in symptoms of anxiety evaluated using the self-assessment questionnaire State part of the State-Trait Anxiety Inventory (STAI)
Change from baseline in sleepiness as measured using the KSS
时间窗: Before the administration and 3 and 7 hours after the administration
Change in sleepiness evaluated using the Karolinska Sleepiness Scale (KSS)
Change from baseline in systemic IL-1B concentrations
时间窗: Before the administration and 1, 1.5, 2, 3, 4, 5, 7 hours after the administration
Change in plasma concentration of the pro-inflammatory cytokine interleukin-1 beta (IL-1B)
Change from baseline in sickness behavior as measured using the sicknessQ
时间窗: Before the administration and 1.5, 3, 5 and 7 hours after the administration
Change in sickness behavior evaluated using the self-assessment questionnaire sicknessQ
Change from baseline in psychological state as measured using the SCAS
时间窗: Before the administration and 3 and 7 hours after the administration
Change in mood alterations evaluated using the self-assessment questionnaire Swedish Core Affect Scales (SCAS)
Change from baseline in systemic IL-6 concentrations
时间窗: Before the administration and 1, 1.5, 2, 3, 4, 5, 7 hours after the administration
Change in plasma concentration of the pro-inflammatory cytokine interleukin-6 (IL-6)
Change from baseline in systemic IL-8 concentrations
时间窗: Before the administration and 1, 1.5, 2, 3, 4, 5, 7 hours after the administration
Change in plasma concentration of the pro-inflammatory cytokine interleukin-8 (IL-8)
Change from baseline in heart rate
时间窗: Before the administration and every half hour up to 7.5 hours after the administration
Change in heart rate assessed using a cardiac monitoring
Change from baseline in headache scores as measured using a numerical scale
时间窗: Before the administration and every half hour up to 7.5 hours after the administration
Change in headache scores measured using a numerical scale ranging from 0 (no headache) to 10 (most unbearable headache)
Change from baseline in systemic IL-10 concentrations
时间窗: Before the administration and 1, 1.5, 2, 3, 4, 5, 7 hours after the administration
Change in plasma concentration of the anti-inflammatory cytokine interleukin-10 (IL-10)
Change from baseline in diastolic blood pressure
时间窗: Before the administration and every half hour up to 7.5 hours after the administration
Change in diastolic blood pressure assessed using a cardiac monitoring
Change from baseline in back pain scores as measured using a numerical scale
时间窗: Before the administration and every half hour up to 7.5 hours after the administration
Change in back pain scores measured using a numerical scale ranging from 0 (no back pain) to 10 (most unbearable back pain)
次要结局
- Change in expression of immune cell markers(Before the administration and 1, 2, 3, 4, 7 hours after the administration)
- Changes in social interaction(During all day)
- Face expression of sickness(Before the administration and 2 and 7.5 hours after)
- Change in skin color(Before the administration and 1,2,3,4,5,7 hours after)
- Change in cell expression of blood microparticles(Before the administration and 1, 1.5, 2, 3, 4, 5, 7 hours after the administration)
- Modification in genetic markers(Before the administration and 1, 2, 4, 7 hours after the administration)
- Change in odor compounds(Before and after the administration)
- Motivation as measured using the Effort Expenditure for Rewards Task (EEfRT)(4 hours after the administration)
- Gait(2 hours after the administration)
- Approach-avoidance behavior(5 hours after the administration)
研究者
Mats Lekander
Professor
Karolinska Institutet