LPS for Alzheimer's Disease

CG
Overseen ByCarol Gunnoud
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how microglia (immune cells in the brain) react in people with Alzheimer's Disease compared to those without it. Participants will receive lipopolysaccharide, a compound used to activate immune cells, to stimulate these brain cells, and researchers will observe the differences. This trial suits individuals diagnosed with mild Alzheimer's Disease who have a caregiver and can consent to participate.

As an Early Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to contribute to groundbreaking insights into Alzheimer's Disease.

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 there any evidence suggesting that lipopolysaccharide is likely to be safe for humans?

Research has shown that lipopolysaccharide (LPS) is generally safe and well-tolerated for studying inflammation in people. A review of 155 studies found that negative side effects were rare, indicating the LPS model's reliability for research. However, LPS triggers a strong inflammatory response, which is why researchers use it in these studies. The dose in this trial is lower than the highest safe dose of 4 ng/kg administered intravenously, ensuring safety for participants.12345

Why do researchers think this study treatment might be promising?

Researchers are excited about this trial because it explores a novel way to understand microglia function in Alzheimer's disease using PBR28 brain PET imaging combined with a lipopolysaccharide (LPS) challenge. Unlike standard Alzheimer's treatments, which typically focus on reducing amyloid plaques or tau tangles, this approach targets the role of microglia, the brain's immune cells, potentially offering new insights into the disease's progression. By using LPS, a component that triggers an immune response, researchers hope to better visualize and understand how microglia activity correlates with Alzheimer's, paving the way for innovative therapeutic strategies.

What evidence suggests that lipopolysaccharide might be an effective treatment for Alzheimer's Disease?

Research shows that a substance called lipopolysaccharide (LPS) can cause inflammation in the body. Animal studies have found that LPS affects memory, particularly the ability to remember locations. It also influences the behavior of certain human cells and gene expression. These effects relate to its role in triggering immune responses, providing insight into its potential impact on brain function. In this trial, participants will receive LPS to study its effects. Although no direct proof exists yet that LPS can treat Alzheimer's, its ability to activate immune cells might offer insights into the disease.678910

Who Is on the Research Team?

AM

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
See 7 more

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?
1Treatment groups
Experimental Treatment
Group I: Patients receiving endotoxinExperimental Treatment1 Intervention

Find a Clinic Near You

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

Bacterial endotoxin-lipopolysaccharide role in inflammatory ...According to published research, prolonged administration of LPS results in impaired spatial memory in SD rats (95). ... Accumulated data also supports that LPS ...
Lipopolysaccharide Endotoxins - PMC - PubMed Central - NIHLipopolysaccharides typically consist of a hydrophobic domain known as lipid A (or endotoxin), a non-repeating “core” oligosaccharide, and a distal ...
Lipopolysaccharide Structure and the Phenomenon of Low ...It is more effective to prevent LPS contamination at the source, rather than trying to sterilise contaminated equipment. LPS is highly resistant to common ...
Bacterial endotoxin lipopolysaccharides regulate gene ...The objective of this study was to survey the effect of LPS on cell viability and gene expression of 55 molecular targets in human colon cancer cells.
The impact of LPS mutants on endotoxin masking in ...Notably, mutants Ra and Rb, possessing shorter polysaccharide chains than the smooth LPS, exhibited recoveries of around 50 % after 45 min. In contrast, all ...
Lipopolysaccharide Safety GuideSafety Data Sheet. LPS can be fatal if swallowed. Please refer to the Safety. Data Sheet (SDS) for additional information. References. B ...
7.pubmed.ncbi.nlm.nih.govpubmed.ncbi.nlm.nih.gov/25655761/
Lipopolysaccharide challenge: immunological effects and ...This article reviews immunogenicity and safety data pertaining to LPS administration, with a particular focus on LPS inhalation, which may facilitate the ...
The Safety of Intravenous Lipopolysaccharide for the Study ...The rarity of adverse events across the 155 studies reviewed suggests that the LPS model of systemic inflammation in humans is safe and well tolerated.
Oral and transdermal administration of lipopolysaccharide ...The maximum-tolerated dose of the intravenous administration of LPS in humans is as low as 4 ng/kg, and it is an extremely strong inflammatory ...
Lipopolysaccharide - General Standard Operating ProcedureReview Safety Data Sheets (SDS) and refer to other general use SOPs relevant ... • Safety glasses (If splash potential exists, use goggles + face shield instead).
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