Healthy
Conditions
Keywords
PET TSPO Imaging, Microglia Activation/Proliferation, Lipopolysaccharide
Brief summary
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.
Interventions
BIOLOGICALLipopolysaccharide
Endotoxin E Coli
Sponsors
Yale University
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1\) Medically-healthy male and female subjects able to read/write English
Exclusion criteria
1. Subjects cannot meet DSM criteria for substance use disorder 2. 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 3. Pregnancy or breastfeeding; 4. Any current medical illness that could put the subjects at risk during the PET scan, or interfere with the PET or immunologic measures 5. 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 6. Subjects taking corticosteroids or other immunosuppressant drugs 7. Subjects with disorders affecting the brain, including but not limited to multiple sclerosis, history of stroke, brain tumors, intracranial bleeding, infection, or abscess.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Baseline TSPO Availability | Before LPS administration (baseline) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Alcohol Dependence Scale (ADS) - questionnaire | baseline | 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 |
Countries
United States
Outcome results
None listed