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Alzheimer Disease, Late OnsetPhase 2NCT04449926

BCG and Plasma Amyloid in Non-Demented Adults

A Phase 2 study testing Bacillus of Calmette and Guerin (BCG) in people with Alzheimer Disease, Late Onset, run by Mindful Diagnostics and Therapeutics, LLC at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

BCG vaccination, the most widely used vaccination in the world, is used to reduce risk of tuberculosis infection; it is used for other mycobacterial infections as well, benefiting leprosy and Buruli ulcer. Read more about this study

Who is it for?
Ages 50 to 80 yearsHealthy volunteers can take part
Conditions the study is for
Alzheimer Disease, Late Onset
What is being tested?
Bacillus of Calmette and Guerin (BCG)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
49 participants
Where
1 siteUnited States
Study dates
9 Nov 2020to 5 Dec 2021
Phase
Phase 2
Are there results?
None posted in the registry

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 50 to 80 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • BCG naive
  • Ability to read, understand and sign consent form

Who cannot join

  • Known allergy to (components of) the BCG vaccine or serious adverse events to prior vaccine administration
  • Known active or latent Mycobacterium tuberculosis or with another mycobacterial species. A history of - or a suspicion of M. tuberculosis infection.
  • Fever (>38 C) within the past 24 hours.
  • Suspicion of active viral or bacterial infection.
  • Vaccination in the past 4 weeks or expected vaccination during the study period, independent of the type of vaccination.
  • Severely immunocompromised subjects. This exclusion category comprises: a) subjects with known infection by the human immunodeficiency virus (HIV-1); b) neutropenic subjects with less than 500 neutrophils/mm3; c) subjects with solid organ transplantation; d) subjects with bone marrow transplantation; e) subjects under chemotherapy; f) subjects with primary immunodeficiency; g) severe lymphopenia with less than 400 lymphocytes/mm3; h) treatment with any anti-cytokine therapies. i) treatment with oral or intravenous steroids defined as daily doses of 10mg prednisone or equivalent for longer than 3 months, or probable use of oral or intravenous steroids in the following four weeks.
  • Active solid or non-solid malignancy or lymphoma within the prior two years.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Mindful Diagnostics and Therapeutics

    Eau Claire, Wisconsin, 54701-3016

Other trials in United States

About this study

BCG vaccination, the most widely used vaccination in the world, is used to reduce risk of tuberculosis infection; it is used for other mycobacterial infections as well, benefiting leprosy and Buruli ulcer. BCG has "heterologous" effects that aids in an array of non-mycobacterial and viral infections as well as bladder cancer. It is the heterologous effect, sometimes called the "off-target" effect that may offer benefit in Alzheimer's disease. Population studies and studies of adults receiving BCG show a lessened risk of Alzheimer's disease. The study will see if BCG vaccination will alter a plasma test for amyloid, a biomarker for cerebral amyloid.

Read the detailed description

Alzheimer's disease (AD) is commonly regarded as Alzheimer's dementia. It is now understood that changes in the brain that result in late-onset AD dementia start years or even decades prior to clinical dementia. Biomarkers aid in diagnosing AD however, currently approved biomarkers have drawbacks as they are invasive and expensive. The two most commonly used biomarkers are amyloid PET scan and spinal tap for amyloid and tau. A new plasma amyloid test has received "Breakthrough Device Designation" from the US-FDA. As an investigational tool, this blood test for amyloid peptides 42/40 levels accurately predicts brain amyloidosis in cognitively normal individuals. In the past 100 years, four billion doses of BCG vaccination have been given for tuberculosis prevention. A favorable effect with BCG for non-tuberculous mycobacteria is also recognized in cervical lymphadeniits, leprosy and Buruli's ulcer. Recently, BCG has found favorable use in autoimmune diseases type 1 diabetes (T1D) and multiple sclerosis (MS); moreover, a protective role by BCG for Alzheimer's disease has been described. Adult exposure to BCG lessened the risk of AD by four-fold. This is an interventional pilot study to test 50 non-demented adults measuring their plasma amyloid 42/40 level prior to BCG prime/boost followed with the same plasma amyloid testing 9 months after vaccination. Sub-clinical CMV infection is felt to drive immune senescence and increase the risk of AD; we will test for CMV antibodies and we will measure lymphocyte phenotype prior to BCG and at study end to look for an immune-modulating effect on this indicator of immunosenescence.

Being tested
Bacillus of Calmette and Guerin (BCG)
Keywords
Alzheimer's disease, biomarker, BCG, plasma amyloid, peptides 42/40, heterologous effect, immune risk profile, CMV, HHV5, immunosenescence
Medical subject headings
Alzheimer Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Bacillus of Calmette and Guerin (BCG)Biological

    Prime and boost vaccination

Study groups in NCT04449926
Study groupRoleWhat they receive
BCG VaccinatedExperimentalExperimental: BCG Group FDA-approved BCG Tice strain, procured from Merck, will be used. The vaccine will be reconstituted according to the package insert. In brief, a vial containing ~1x10^8 CFU of lyophilized BCG will be reconstituted in 50 mL of saline. A single dose will consist of 0.1 mL (~2x10^5 CFU) will be administered by slow intradermal injection using a 25 gauge/ 0.5 mm syringe in the deltoid area. A follow up "booster" dose will be given one month after the initial dose.
Receives: Biological: Bacillus of Calmette and Guerin (BCG)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in Plasma Amyloid

    Level of Plasma Peptides 42/40 pre-BCG vaccination are compared with levels nine months post vaccination

    Measured: 9 months

Secondary outcomes (1)

  1. Change in Immune Risk Profile

    T-cell phenotype: CD4:CD8 ratios are measured pre-BCG vaccination and nine months post vaccination.

    Measured: nine months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Jun 2020
  2. Study start9 Nov 2020
  3. Primary completion4 Dec 2021
  4. Study completion5 Dec 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Prevention
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
49 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04449926
Sponsor's protocol ID
BCG-PANDA 01
Status last verified
Dec 2021
First submitted
24 Jun 2020
Last updated
23 Dec 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Schindler SE, Bollinger JG, Ovod V, Mawuenyega KG, Li Y, Gordon BA, Holtzman DM, Morris JC, Benzinger TLS, Xiong C, Fagan AM, Bateman RJ. High-precision plasma beta-amyloid 42/40 predicts current and future brain amyloidosis. Neurology. 2019 Oct 22;93(17):e1647-e1659. doi: 10.1212/WNL.0000000000008081. Epub 2019 Aug 1.

    PubMed 31371569

  • Gofrit ON, Klein BY, Cohen IR, Ben-Hur T, Greenblatt CL, Bercovier H. Bacillus Calmette-Guerin (BCG) therapy lowers the incidence of Alzheimer's disease in bladder cancer patients. PLoS One. 2019 Nov 7;14(11):e0224433. doi: 10.1371/journal.pone.0224433. eCollection 2019.

    PubMed 31697701

  • Gofrit ON, Bercovier H, Klein BY, Cohen IR, Ben-Hur T, Greenblatt CL. Can immunization with Bacillus Calmette-Guerin (BCG) protect against Alzheimer's disease? Med Hypotheses. 2019 Feb;123:95-97. doi: 10.1016/j.mehy.2019.01.007. Epub 2019 Jan 11.

    PubMed 30696606

  • Dow CT. Proposing BCG Vaccination for Mycobacterium avium ss. paratuberculosis (MAP) Associated Autoimmune Diseases. Microorganisms. 2020 Feb 5;8(2):212. doi: 10.3390/microorganisms8020212.

    PubMed 32033287

  • Lurain NS, Hanson BA, Martinson J, Leurgans SE, Landay AL, Bennett DA, Schneider JA. Virological and immunological characteristics of human cytomegalovirus infection associated with Alzheimer disease. J Infect Dis. 2013 Aug 15;208(4):564-72. doi: 10.1093/infdis/jit210. Epub 2013 May 9.

    PubMed 23661800

  • Westman G, Berglund D, Widen J, Ingelsson M, Korsgren O, Lannfelt L, Sehlin D, Lidehall AK, Eriksson BM. Increased inflammatory response in cytomegalovirus seropositive patients with Alzheimer's disease. PLoS One. 2014 May 7;9(5):e96779. doi: 10.1371/journal.pone.0096779. eCollection 2014.

    PubMed 24804776

  • Luz Correa B, Ornaghi AP, Cerutti Muller G, Engroff P, Pestana Lopes R, Gomes da Silva Filho I, Bosch JA, Bonorino C, Bauer ME. The inverted CD4:CD8 ratio is associated with cytomegalovirus, poor cognitive and functional states in older adults. Neuroimmunomodulation. 2014;21(4):206-12. doi: 10.1159/000356827. Epub 2014 Feb 6.

    PubMed 24504177

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Bacillus of Calmette and Guerin (BCG) in people with Alzheimer Disease, Late Onset, run by Mindful Diagnostics and Therapeutics, LLC at 1 site in United States.

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 2 inclusion and 7 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: finished, as of the sponsor's last update on 23 Dec 2021. 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 United States. 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?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Change in Plasma Amyloid (time frame: 9 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04449926, which also lists 7 linked publications.

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 23 Dec 2021.

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