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Neuroimmune Response to Lipopolysaccharide

Sponsor
Yale University (Other)
Overall Status
Completed
CT.gov ID
NCT04233593
Collaborator
(none)
27
Enrollment
1
Location
2
Arms
88.8
Actual Duration (Months)
0.3
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Biological: Lipopolysaccharide
 Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
27 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
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.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)
Primary Purpose:
Basic Science
Official Title:
Imaging the Neuroimmune Response to Lipopolysaccharide
Actual Study Start Date :
Mar 25, 2014
Actual Primary Completion Date :
Aug 17, 2021
Actual Study Completion Date :
Aug 17, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: LPS Challenge

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
Endotoxin E Coli
Other Names:
  • LPS

    		•
    No Intervention: LPS Follow-up

    Subjects will undergo one 120-minute [11C]PBR28 PET scan 24+ hours after LPS.

    Outcome Measures

    Primary Outcome Measures

    1. 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 Outcome Measures

    1. 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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 55 Years
    Sexes Eligible for Study:
    All
    Accepts 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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Yale University New Haven Connecticut United States 06519

    Sponsors and Collaborators

    • Yale University

    Investigators

    • Principal Investigator: Kelly Cosgrove, PhD, Yale University

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Kelly Cosgrove, Associate Professor, Yale University
    ClinicalTrials.gov Identifier:
    NCT04233593
    Other Study ID Numbers:
    • 1305011987
    First Posted:
    Jan 18, 2020
    Last Update Posted:
    Jul 19, 2022
    Last Verified:
    Jun 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Kelly Cosgrove, Associate Professor, Yale University
    PET TSPO Imaging
    Microglia Activation/Proliferation
    Lipopolysaccharide

    Study Results

    No Results Posted as of Jul 19, 2022