Clinical trial NCT06620679: Mapping the Effect of (neuro)inflammation on Stress Sensitivity in the Brain of Healthy Men
Official title: Mapping the Effect of (neuro)inflammation on Stress Sensitivity in the Brain of Healthy Men
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Inflammation
Stress
Healthy Volunteer
Keywords: Inflammation
Stress
Lipopolysaccharide (LPS)
Short-chain fatty acids
Neuroimaging
Lead sponsor: Universitaire Ziekenhuizen KU Leuven
Sponsor class: OTHER
First posted: 2024-10-01
Enrollment: 20
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Male
* Healthy
* Age 18-45 years
* BMI 18.5-25 kg/m2
* Proficient in English and/or Dutch

Exclusion Criteria:

* 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

Primary outcomes:
measure: Blood-oxygenation-level-dependent functional magnetic resonance imaging (BOLD fMRI) response to acute stress task
timeFrame: 2 hours after the single i.v bolus administration of LPS or saline
measure: Binding potential of [18F]-DPA-714 radiotracer
timeFrame: 2 hours after the single i.v bolus administration of LPS or saline
Secondary outcomes:
measure: Concentration of serum cytokines
timeFrame: From 1 hour prior to intervention to 6 hours post-intervention
measure: Concentration of serum C-reactive protein (CRP)
timeFrame: From 1 hour prior to intervention to 24 hours post-intervention
measure: Concentration of serum free cortisol
timeFrame: From 1 hour prior to intervention to 24 hours post-intervention
measure: Concentration of plasma Adrenocorticotropic Hormone (ACTH)
timeFrame: From 1 hour prior to intervention to 24 hours post-intervention
measure: Pulse rate
timeFrame: From 1 hour prior to intervention to 6 hours post-intervention
measure: Systolic blood pressure
timeFrame: From 1 hour prior to intervention to 6 hours post-intervention
measure: Diastolic blood pressure
timeFrame: From 1 hour prior to intervention to 6 hours post-intervention
measure: Body temperature
timeFrame: From 1 hour prior to intervention to 6 hours post-intervention
measure: Scoring of the Generic Assessment of Side Effects (GASE) questionnaire
timeFrame: From 1 hour prior to intervention to 7 days post-intervention
measure: Scoring of the Sickness Questionnaire (SicknessQ)
timeFrame: From 1 hour prior to intervention to 24 hours post-intervention
measure: Scoring of the State-Trait Anxiety Inventory, State Anxiety subscale (STAI-S)
timeFrame: From 1 hour prior to intervention to 24 hours post-intervention
measure: Scoring of the State-Trait-Anxiety and Depression Scale (STADI)
timeFrame: From 1 hour prior to intervention to 24 hours post-intervention
measure: Scoring of the Stanford Sleepiness Scale (SSS)
timeFrame: From 1 hour prior to intervention to 24 hours post-intervention
measure: Scoring of the Positive and Negative Affect Schedule (PANAS)
timeFrame: From 1 hour prior to intervention to 24 hours post-intervention
measure: Scoring of the Multidimensional Mood Questionnaire (MDMQ)
timeFrame: From 1 hour prior to intervention to 24 hours post-intervention
Other outcomes:
measure: Concentration of serum short-chain fatty acids (SCFAs)
timeFrame: From 1 hour prior to intervention to 6 hours post-intervention
measure: Quantitative profile of microbiota
timeFrame: On each intervention/placebo day
measure: Scoring of the Bristol Stool Score (BSS)
timeFrame: On each intervention/placebo day
Locations:
city: Leuven
country: Belgium
facility: UZ/KU Leuven
state: Flemish Brabant
Study officials:
affiliation: KU Leuven
name: Lukas Van Oudenhove, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: KU Leuven
name: Kristin Verbeke, Pharm, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: KU Leuven
name: Boushra Dalile, PhD
role: PRINCIPAL_INVESTIGATOR
References: