Neuroimmune Response to Lipopolysaccharide

Imaging the Neuroimmune Response to Lipopolysaccharide

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Biological: Lipopolysaccharide

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Yale University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Yale University

Study record dates

Study Major Dates

• Study Start (Actual): March 25, 2014
• Primary Completion (Actual): August 17, 2021
• Study Completion (Actual): August 17, 2021

Study Registration Dates

• First Submitted: January 11, 2020
• First Submitted That Met QC Criteria: January 16, 2020
• First Posted (Actual): January 18, 2020

Study Record Updates

• Last Update Posted (Actual): July 19, 2022
• Last Update Submitted That Met QC Criteria: July 14, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: Lipopolysaccharide; PET TSPO Imaging; Microglia Activation/Proliferation
• Other Study ID Numbers: 1305011987

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No