Peripheral Benzodiazepine Receptors (PBR28) Brain PET Imaging With Lipopolysaccharide Challenge for the Study of Microglia Function in Alzheimer's Disease

Overseen By Carol Gunnoud

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Yale University

Must not be taking: Corticosteroids, Immunosuppressants, Antiplatelets, Anticoagulants

Disqualifiers: Neurologic disease, Systemic disease, Psychiatric disorder, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 1 day

18 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial measures microglial activity in Alzheimer's patients and compares it to healthy older adults. It aims to understand why some people with brain changes typical of Alzheimer's develop dementia while others do not. Microglia are brain cells that help with immune responses, and their activity might be linked to Alzheimer's symptoms.

Will I have to stop taking my current medications?

The trial requires that you stop using over-the-counter medications that may affect the immune system, like ibuprofen, and corticosteroids or immunosuppressant drugs at least 3 weeks before the PET scan. Investigational agents are also prohibited 4 weeks prior to entry and during the study.

Is lipopolysaccharide safe for humans?

The research does not provide specific safety data for lipopolysaccharide in humans, but it mentions that lipopolysaccharide from bacteria can trigger strong inflammatory responses, which may be a concern for safety. ^{1 2 3 4 5}

How does this drug differ from other treatments for bacterial infections?

This drug is unique because it targets lipopolysaccharides (LPS), which are major components of the outer membrane of Gram-negative bacteria, playing a crucial role in their defense against antibiotics. By focusing on LPS, this drug may offer a novel approach to overcoming bacterial resistance and enhancing the effectiveness of existing antibiotics. ^{3 6 7 8 9}

What data supports the effectiveness of the treatment Lipopolysaccharide?

Research suggests that methods to reduce lipopolysaccharide (LPS) levels, such as using an LPS adsorber, can improve outcomes in severe sepsis by lowering LPS and inflammatory markers in the blood, leading to better patient recovery. ^{10 11 12 13 14}

Who Is on the Research Team?

Adam Mecca, M.D., Ph.D.

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

Inclusion Criteria

National Institute on Aging (NIA)-Alzheimer's Association core clinical criteria for probable AD

Age between 55 and 90 (inclusive)

Score on the Montreal Cognitive Assessment (MOCA) greater than or equal to 17

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive LPS (0.4 ng/kg) administered intravenously and undergo PET scanning

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Lipopolysaccharide

How Is the Trial Designed?

Group I: Patients receiving endotoxin Experimental Treatment 1 Intervention

The 20 enrolled subjects will have LPS (0.4 ng/kg) administered intravenously

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Citations

1. South Africa pubmed.ncbi.nlm.nih.gov

Anti-endotoxin in the treatment of severe surgical septic shock. Results of a randomized double-blind trial. [2014]

2. United States pubmed.ncbi.nlm.nih.gov

Tumor necrosis factor alone does not explain the lethal effect of lipopolysaccharide. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Use of an endotoxin adsorber in the treatment of severe abdominal sepsis. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Lipid A analogs aimed at preventing the detrimental effects of endotoxin. [2005]

5. United States pubmed.ncbi.nlm.nih.gov

Comparable endotoxic properties of lipopolysaccharides are manifest in diverse clinical isolates of gram-negative bacteria. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Human antiserum for prevention of the local shwartzman reaction and death from bacterial lipopolysaccharides. [2018]

7. England pubmed.ncbi.nlm.nih.gov

Results of a harmonized endotoxin recovery study protocol evaluation by 14 BioPhorum Operations Group (BPOG) member companies. [2019]

8. England pubmed.ncbi.nlm.nih.gov

On the essentiality of lipopolysaccharide to Gram-negative bacteria. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Measurement of endotoxin activity in critically ill patients using whole blood neutrophil dependent chemiluminescence. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

Evidence against a bacterial endotoxin masking effect in biologic drug products by limulus amebocyte lysate detection. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

The diversity of the core oligosaccharide in lipopolysaccharides. [2010]

12. England pubmed.ncbi.nlm.nih.gov

The structures of core regions from enterobacterial lipopolysaccharides - an update. [2007]

13. United States pubmed.ncbi.nlm.nih.gov

Bacterial lipopolysaccharides and innate immunity. [2022]

14. England pubmed.ncbi.nlm.nih.gov

Structural determination of lipid A from gram negative bacteria using laser desorption mass spectrometry. [2007]