Mapping the Effect of (neuro)inflammation on Stress Sensitivity in the Brain of Healthy Men
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Blood-oxygenation-level-dependent functional magnetic resonance imaging (BOLD fMRI) response to acute stress task
研究概览
简要总结
The goal of this interventional study is to determine the effects of inflammation on stress responses in the brain of healthy men. In order to achieve this goal, participants are injected with an inflammation-inducing agent, then observed inside a brain scanner.
详细描述
This interventional study is a randomized, triple-blind, placebo-controlled, cross-over study aiming to elucidate the impact of acute laboratory-induced inflammation using lipopolysaccharide (LPS) on stress responses in the brain of healthy men. Acute stress responses to a psychological task, the Maastricht Imaging Stress Task (MIST), are observed via blood-oxygenation-level-dependent functional magnetic resonance imaging (BOLD fMRI) and simultaneous positron emission tomography (PET) imaging using the radiotracer 18 Fluor (18F)-N,N-diethyl-2-[4-(2-fluoroethoxy)phenyl]-5,7-dimethylpyrazole[1,5-a]pyrimidine-3-acetamide (DPA)-714, which targets the 18 kilodalton (kDA) translocator protein (TSPO) of activated microglia. Every participant will receive 0.4 ng/kg body weight of LPS and saline on separate treatment visits, separated by a 2-3 months wash-out period.
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 45 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Age 18-45 years
- •BMI 18.5-25 kg/m2
- •Proficient in English and/or Dutch
排除标准
- •Have previous or current neuropsychiatric disorders or have history of major head trauma
- •Have any disorder, which in the Investigator's opinion might jeopardise your safety or compliance with the study
- •Have any prior or current treatment(s) that might jeopardise your safety or that would compromise the integrity of the study
- •Have any prior and recent medication use (especially antibiotics, cardiovascular drugs, steroids, non-steroid anti-inflammatory drugs, centrally effective drugs)
- •Are participating in an interventional Trial with an investigational medicinal product (IMP) or device
- •Have current or previous infection or vaccination within the last 8 weeks
- •Have pathological values of blood indices and certain genetic profiles that will affect brain imaging results (we will conduct a blood screening before starting the study)
- •Had strong physical activity (e.g. swimming, football, running more than 8 km per hour, carrying heavy loads) 24h before the start of the experiment.
- •Are a smoker
- •Are a night-shift worker
- •Have recent or previous use of psychotropics within the last year
- •Have regular high alcohol use (>4 drinks/week)
- •Have any brain imaging contraindications:
- •Have claustrophobia or too much uneasiness in limited spaces (in order to tolerate confinement during the scanning procedures).
- •Have severe back problems that will interfere with lying on your back in the scanner with no movement for long durations.
- •Have any condition that would interfere with MRI studies (e.g., cochlear implant, metal fragments in eyes, cardiac pacemaker, neural stimulator, and metallic body inclusion or other metal implanted in the body). To check this, you will need to fill out a checklist before the procedure.
- •You and/or your partner is planning to become pregnant during and up to one month of the completion of the study
研究组 & 干预措施
LPS then Saline
A crossover arm where the participant first receives the intervention (LPS), undergoes a wash-out period, then receives the placebo (saline).
干预措施: Lipopolysaccharide (LPS) (Biological)
LPS then Saline
A crossover arm where the participant first receives the intervention (LPS), undergoes a wash-out period, then receives the placebo (saline).
干预措施: Placebo (Other)
Saline then LPS
A crossover arm where the participant first receives the placebo (saline), undergoes a wash-out period, then receives the intervention (LPS).
干预措施: Lipopolysaccharide (LPS) (Biological)
Saline then LPS
A crossover arm where the participant first receives the placebo (saline), undergoes a wash-out period, then receives the intervention (LPS).
干预措施: Placebo (Other)
结局指标
主要结局
Blood-oxygenation-level-dependent functional magnetic resonance imaging (BOLD fMRI) response to acute stress task
时间窗: 2 hours after the single i.v bolus administration of LPS or saline
BOLD fMRI responses to the Montreal Imaging Stress Task (MIST) after administration of LPS compared to saline
Binding potential of [18F]-DPA-714 radiotracer
时间窗: 2 hours after the single i.v bolus administration of LPS or saline
The change in \[18F\]-DPA-714 binding potential with and without LPS administration (%∆BPND)
次要结局
- Concentration of serum cytokines(From 1 hour prior to intervention to 6 hours post-intervention)
- Concentration of serum C-reactive protein (CRP)(From 1 hour prior to intervention to 24 hours post-intervention)
- Concentration of serum free cortisol(From 1 hour prior to intervention to 24 hours post-intervention)
- Concentration of plasma Adrenocorticotropic Hormone (ACTH)(From 1 hour prior to intervention to 24 hours post-intervention)
- Pulse rate(From 1 hour prior to intervention to 6 hours post-intervention)
- Systolic blood pressure(From 1 hour prior to intervention to 6 hours post-intervention)
- Diastolic blood pressure(From 1 hour prior to intervention to 6 hours post-intervention)
- Body temperature(From 1 hour prior to intervention to 6 hours post-intervention)
- Scoring of the Generic Assessment of Side Effects (GASE) questionnaire(From 1 hour prior to intervention to 7 days post-intervention)
- Scoring of the Sickness Questionnaire (SicknessQ)(From 1 hour prior to intervention to 24 hours post-intervention)
- Scoring of the State-Trait Anxiety Inventory, State Anxiety subscale (STAI-S)(From 1 hour prior to intervention to 24 hours post-intervention)
- Scoring of the State-Trait-Anxiety and Depression Scale (STADI)(From 1 hour prior to intervention to 24 hours post-intervention)
- Scoring of the Stanford Sleepiness Scale (SSS)(From 1 hour prior to intervention to 24 hours post-intervention)
- Scoring of the Positive and Negative Affect Schedule (PANAS)(From 1 hour prior to intervention to 24 hours post-intervention)
- Scoring of the Multidimensional Mood Questionnaire (MDMQ)(From 1 hour prior to intervention to 24 hours post-intervention)
研究者
Lukas Van Oudenhove
Principal Investigator
Universitaire Ziekenhuizen KU Leuven