Alzheimer Disease, Late OnsetEarly Phase 1BCG-ADNCT06078891
Does BCG Vaccination Reduce Biomarkers of Alzheimer's Disease?
A Early Phase 1 study testing BCG vaccine in people with Alzheimer Disease, Late Onset, run by Tamir Ben-Hur at 1 site in Israel.
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. Read more about this study
- Who is it for?
- Ages 70 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Alzheimer Disease, Late Onset
- What is being tested?
- BCG vaccine
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteIsrael
- Study dates
- 1 Jul 2023to 31 Dec 2025
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 70 to 80 years
- All sexes
- Healthy volunteers accepted
- Older adult
Who may be able to join
- 70-80 years old patients with self-reported preserved cognitive function and instrumental activities of daily life (iADL).
- MoCA score of ≥26.
- Increased plasma p-tau181 level.
Who cannot join
- Extrapyramidal signs, documented CVA, existence of multi-infarct dementia or fronto-temporal dementia according to clinical impression by treating cognitive neurologist.
- Active cancer, severe cardio-pulmonary disease or other medical condition which negatively affects ability to evaluate patients and complete follow-up.
- Active glucocorticoids treatment, chronic immunosuppressive medications, or currently living with an immunosuppressed individual to prevent an adverse event from the administration of this live vaccine.
- Above 10mm induration diameter at 48 hours after initial PPD test.
- Inability to sign an informed consent due to psychiatric or dementing condition.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
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:
Read more
- 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.
Read the detailed 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.
- Conditions
- Alzheimer Disease, Late Onset
- Being tested
- BCG vaccine
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BCG vaccineBiological
Three intra-dermal vaccinations over a period of one year.
| Study group | Role | What they receive |
|---|---|---|
| BCG vaccinated patients | Experimental | A single arm experiment to examine the effect of 3 standard intradermal vaccinations with BCG (at times 0, 1 month and 12 months) on plasma biomarkers. Receives: Biological: BCG vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma phosphorylated Tau (p-tau181) biomarker level, measured in picogram/ml by SIMOA technology.
Four measurements of plasma p-tau181 levels (range 1-100 picogram/ml)
Measured: 1.5 years
Secondary outcomes (2)
Cognitive deterioration by Montreal Cognitive Assessment (MoCA) test
Cognitive evaluation by MoCA test (score 0-30) at recruitment and after 1.5 years
Measured: 1.5 years
Plasma neurofilament-light levels by SIMOA technology
Two measurements of neurofilament-light levels (range 1-100 picogram/ml) by SIMOA technology
Measured: 1.5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Oct 2023
- Study start1 Jul 2023
- Primary completion31 Dec 2025 (estimated)
- Study completion31 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alzheimer Disease, Late OnsetStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- A single group in treated patients to follow changes in plasma biomarkers levels.
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tamir Ben-Hur
- Sponsor type
- University, hospital or other
- Collaborators
- Hebrew University of Jerusalem
- Responsible party
- Sponsor-investigator, Tamir Ben-Hur, Hadassah Medical Organization
- Investigators
- Tamir Ben Hur, MD PhD, Principal investigator, Hadassah Medical Organization
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06078891
- Sponsor's protocol ID
- BCG-AD HMO-CTIL
- Acronym
- BCG-AD
- Status last verified
- Mar 2025
- First submitted
- 6 Aug 2023
- Last updated
- 18 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Does BCG Vaccination Reduce Biomarkers of Alzheimer's Disease?
- ClinicalTrials.gov ID
- NCT06078891
- Acronym / sponsor ID
- BCG-AD / BCG-AD HMO-CTIL
- Conditions
- Alzheimer Disease, Late Onset
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Enrolling by invitation
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Tamir Ben-HurUniversity, hospital or other
- Collaborators
- Hebrew University of Jerusalem
- Study start
- 1 Jul 2023 (actual)
- Primary completion
- 31 Dec 2025 (estimated)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 12 Oct 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- A single group in treated patients to follow changes in plasma biomarkers levels.
| Arm | Type | Receives |
|---|---|---|
| BCG vaccinated patients | Experimental | Biological: BCG vaccineA single arm experiment to examine the effect of 3 standard intradermal vaccinations with BCG (at times 0, 1 month and 12 months) on plasma biomarkers. |
Who may qualify
- Ages
- 70 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Older adult
Key inclusion criteria (3 listed)
- 70-80 years old patients with self-reported preserved cognitive function and instrumental activities of daily life (iADL).
- MoCA score of ≥26.
- Increased plasma p-tau181 level.
Key exclusion criteria (5 listed)
- Extrapyramidal signs, documented CVA, existence of multi-infarct dementia or fronto-temporal dementia according to clinical impression by treating cognitive neurologist.
- Active cancer, severe cardio-pulmonary disease or other medical condition which negatively affects ability to evaluate patients and complete follow-up.
- Active glucocorticoids treatment, chronic immunosuppressive medications, or currently living with an immunosuppressed individual to prevent an adverse event from the administration of this live vaccine.
- Above 10mm induration diameter at 48 hours after initial PPD test.
- Inability to sign an informed consent due to psychiatric or dementing condition.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BCG vaccineThree intra-dermal vaccinations over a period of one year. | Biological | BCG vaccinated patients |
Primary outcome
Plasma phosphorylated Tau (p-tau181) biomarker level, measured in picogram/ml by SIMOA technology.
Time frame: 1.5 years
Four measurements of plasma p-tau181 levels (range 1-100 picogram/ml)
2 secondary outcomes
Cognitive deterioration by Montreal Cognitive Assessment (MoCA) test
Time frame: 1.5 years
Plasma neurofilament-light levels by SIMOA technology
Time frame: 1.5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Mar 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Tamir Ben Hur, MD PhD principal investigator
Hadassah Medical Organization
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing BCG vaccine in people with Alzheimer Disease, Late Onset, run by Tamir Ben-Hur at 1 site in Israel.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: enrolling by invitation, as of the sponsor's last update on 18 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Plasma phosphorylated Tau (p-tau181) biomarker level, measured in picogram/ml by SIMOA technology. (time frame: 1.5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Mar 2025.