Neuroimmune Response to Lipopolysaccharide

Study Overview
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Brief Summary
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In this study, healthy adult volunteers will undergo two positron emission tomography (PET) scans using the radiotracer [11C]PBR28 which binds to the 18kDa translocator protein (TSPO). Approximately 3 hours prior to the second [11C]PBR28 PET scan, lipopolysaccharide (LPS; endotoxin) will be administered to evoke a robust neuroimmune response. Subjects will also undergo behavioral and cognitive testing. Vital signs, subjective response, and peripheral cytokine levels will be assayed periodically throughout the experimental session. Specific aims: Quantify the magnitude of neuroimmune response after a classical immune stimulus. Secondary aims: Quantify changes in cognitive function after a classical immune stimulus. Hypothesis: Individuals will exhibit a robust whole-brain neuroimmune response and impaired cognitive function after LPS.

Official Title
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Imaging the Neuroimmune Response to Lipopolysaccharide

Conditions
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Healthy

Intervention / Treatment
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* Biological: Lipopolysaccharide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1) Medically-healthy male and female subjects able to read/write English Exclusion Criteria: Subjects cannot meet DSM criteria for substance use disorder Any psychiatric symptoms that could put the subject at risk by participating in the study including but not limited to suicidal or homicidal ideation, or suicide attempt within the last year Pregnancy or breastfeeding; Any current medical illness that could put the subjects at risk during the PET scan, or interfere with the PET or immunologic measures Significant hepatocellular injury (as evidenced by AST or ALT levels greater than 5 times normal or a history of cirrhosis) will be exclusionary in order to reduce the risks associated with alcohol consumption Subjects taking corticosteroids or other immunosuppressant drugs Subjects with disorders affecting the brain, including but not limited to multiple sclerosis, history of stroke, brain tumors, intracranial bleeding, infection, or abscess.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: All subjects will complete one 120-minute [11C]PBR28 PET scan before and one scan 3-hours after lipopolysaccharide (LPS; 1.0ng/kg; IV) administration. A subset of subjects will complete a follow-up [11C]PBR28 PET scan 24+ hours after LPS.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LPS Challenge<br>Subjects will undergo one 120-minute [11C]PBR28 PET scan before and one scan 3-hours after LPS administration (1.0ng/kg; IV). | Biological: Lipopolysaccharide<br>* Endotoxin E Coli<br>* Other names: LPS;|
| No Intervention: LPS Follow-up<br>Subjects will undergo one 120-minute [11C]PBR28 PET scan 24+ hours after LPS. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Baseline TSPO Availability | Time-activity curves will be extracted from brain regions of interest and analyzed using multilinear analysis-1 (t*=30) incorporating the metabolite-corrected arterial input function to yield [11C]PBR28 total volumes of distribution (VT) across brain regions. | Before LPS administration (baseline) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alcohol Dependence Scale (ADS) - questionnaire | self-report questionnaire to determine severity of alcohol symptoms, 25 question multiple choice scale, range of 0-47 for a total score, with higher numbers indicating worse severity | baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PET TSPO Imaging, Microglia Activation/Proliferation, Lipopolysaccharide