Clinical Trial Details
— Status: Enrolling by invitation
Administrative data
NCT number |
NCT06078891 |
Other study ID # |
BCG-AD HMO-CTIL |
Secondary ID |
|
Status |
Enrolling by invitation |
Phase |
Early Phase 1
|
First received |
|
Last updated |
|
Start date |
July 1, 2023 |
Est. completion date |
December 31, 2025 |
Study information
Verified date |
October 2023 |
Source |
Hadassah Medical Organization |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial Summary
The goal of this clinical trial is to test whether vaccination with the BCG vaccine may
improve the blood level of a biomarker of Alzheimer's disease (AD) in participants who are
cognitively- and functionally- intact elderly (70-80 years old) participants, who display
pathologically high levels of the blood biomarker.
The main questions it aims to answer are:
- Does BCG vaccination lower the plasma level of phosphorylated Tau protein (p-tau181).
- Do vaccinated participants remains stable cognitively.
Participants will be asked to:
- Undergo cognitive and behavioral evaluation.
- Receive 3 BCG vaccinations over the course of 1 year.
- Perform blood tests on several occasions. All participants will be treated and followed.
Description:
Brain accumulation of insoluble Beta-Amyloid and of hyperphosphorylated tau protein -rich
neurofibrillary tangles in Alzheimer's disease (AD), accompanied by oxidative stress and
sustained inflammation develops approximately 20 years before appearance of symptomatic
dementia. These years should be regarded as an incubation period of a deadly condition during
which early therapeutic intervention may increase the likelihood of obtaining a significant
disease modifying effect. Early diagnosis at the pre-symptomatic stage has been hindered by
the lack of reliable, inexpensive and non-invasive biomarkers of disease. Recent developments
have enabled the measurement of plasma p-tau181 level, which has almost 90% sensitivity and
specificity for diagnosing AD. As these biomarkers identify AD pathology prior to clinical
presentation, they enable identifying pre-symptomatic patients, with potential of early
intervention. P-tau181, neurofilament light (NfL) and GFAP biomarkers may also serve as
outcome measures, corresponding to the severity of active neurodegenerative disease in AD.
The investigators propose to select 60 individuals who are at high risk for developing AD
dementia for a single-arm prospective intervention study, by screening cognitively- and
functionally-intact elderly population with non-genetic AD risk factors (around 250
individuals, 70-79 years old) for high plasma p-tau181 level. The current lack of any disease
modifying drug in AD urged them to test if BCG vaccination can prevent, or at least postpone
AD. The rationale is based on multiple scientific observations and on the dramatic reduction
(by 30-50%) in development of dementia in elderly patients with bladder cancer who were
treated with multiple intra-vesicular BCG instillations. Accumulating data argue for the
critical role of the immune system in the course of AD. BCG through its immune-modulation
properties (Tregs, pDCs and IL10 enhancement, M1:M2 macrophage balance) may mitigate the
inflammatory process component of AD and therefore may prevent or delay full blown AD.
In this single arm prospective study, three BCG vaccinations will be provided to the 60
recruited participants over one year. At recruitment and at three times during the two years'
study period, they will be tested for plasma p-tau181 level, and for plasma Nfl and/or GFAP
using SIMOA technology. The baseline p-tau181 will serve as a reference value for monitoring
individual response to the BCG vaccinations during the study, as well as the group trend for
the total Tau biomarker. The investigators will also study the effect of BCG vaccination on
the dynamics of the cognitive performance of the selected individuals.
The investigators hypothesize that BCG vaccination in individuals with high-risk
pre-symptomatic Alzheimer's disease will reduce active brain disease, as determined by blood
biomarkers' levels and will mitigate cognitive decline.