Neuroimmune Response to Lipopolysaccharide

NCT04233593 | Completed Phase 1 FDA Drug

• 1 other identifier: 1305011987
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Keywords

PET TSPO Imaging; Microglia Activation/Proliferation; Lipopolysaccharide

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Alcohol Dependence Scale (ADS) - questionnaire

  baseline

Study Arms (2)

LPS Challenge

EXPERIMENTAL

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

LPS Follow-up

NO INTERVENTION

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

Interventions

Lipopolysaccharide BIOLOGICAL

Endotoxin E Coli

Also known as: LPS

LPS Challenge

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• \) Medically-healthy male and female subjects able to read/write English

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Yale University: lead

Study Sites (1)

Yale University

New Haven, Connecticut, 06519, United States

Location

MeSH Terms

Interventions

Lipopolysaccharides

Intervention Hierarchy (Ancestors)

Glycoconjugates; Carbohydrates; Polysaccharides, Bacterial; Polysaccharides; Lipids; Antigens, Bacterial; Antigens; Biological Factors; Endotoxins; Bacterial Toxins; Toxins, Biological

Study Officials

• Kelly Cosgrove, PhD

  Yale University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: 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.

Study Record Dates

• First Submitted: January 11, 2020
• First Posted: January 18, 2020
• Study Start: March 25, 2014
• Primary Completion: August 17, 2021
• Study Completion: August 17, 2021
• Last Updated: July 19, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)