Brief Title: BCG and Plasma Amyloid in Non-Demented Adults

INTRODUCTION

• Org Study ID: BCG-PANDA 01
• Secondary ID: N/A
• NTC ID: NCT04449926
• Sponsor: Mindful Diagnostics and Therapeutics, LLC

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.

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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.

• Overall Status
  Recruiting
• Start Date
  January 9, 2021
• Phase
  Phase 2
• Study Type
  Interventional