Clinical trial NCT04449926: BCG and Plasma Amyloid in Non-Demented Adults
Official title: BCG and Plasma Amyloid in Non-Demented Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Alzheimer Disease, Late Onset
Keywords: Alzheimer's disease
biomarker
BCG
plasma amyloid
peptides 42/40
heterologous effect
immune risk profile
CMV
HHV5
immunosenescence
Lead sponsor: Mindful Diagnostics and Therapeutics, LLC
Sponsor class: INDUSTRY
First posted: 2020-06-29
Enrollment: 49
Sex: ALL
Minimum age (years): 50
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief 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. 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.

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.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Change in Plasma Amyloid
timeFrame: 9 months
Secondary outcomes:
measure: Change in Immune Risk Profile
timeFrame: nine months
Other outcomes:
Locations:
city: Eau Claire
country: United States
facility: Mindful Diagnostics and Therapeutics
state: Wisconsin
Study officials:
affiliation: Mindful Diagnostics and Therapeutics
name: Coad T Dow, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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