A Pilot Study of the Effects of BCG Immunization on CSF and Blood-based Biomarkers in Older Adults.
Condition: Healthy
Intervention: Bacillus Calmette-Guerin (BCG)
Intervention description: Vaccine
Intervention MeSH terms: BCG Vaccine
Phase: Phase 2
Study type: Interventional
Primary purpose: Other
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: All
Minimum age: 55 Years
Maximum age: 80 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Cognition; Alzheimer's disease; Memory; BCG; Immunization

Summary:

      A pilot study of the effects of Bacillus Calmette-Guérin (BCG) immunization on cerebrospinal
      fluid and blood-based biomarkers in older adults.
    

Eligibility criteria:

        Inclusion Criteria:

        Study subjects meeting all the following criteria will be allowed to enroll in the study:

          1. Age 55-80 inclusive;

          2. Montreal Cognitive Assessment (MoCA ) ≥18;

          3. Normal cognition as defined by Montreal Cognitive Assessment (MoCA) ≥ 26 or Mild
             Cognitive Impairment (MCI) as defined by the National Institute of Health Alzheimer's
             Association (NIA-AA) Workgroup (2011) and MoCA score between 18 and 25 (inclusive);

          4. Education level, English language skills, and literacy indicates subject will be able
             to complete all assessments;

          5. Ability to provide informed consent;

          6. Willing and able to complete all assessment and study procedures, including blood
             draws, lumbar punctures, and clinical assessments;

          7. If on cholinesterase inhibitor and/or memantine, doses are stable for 3 months prior
             to baseline;

          8. Negative test results for Human Immunodeficiency Virus (HIV) antibody and Tuberculosis
             (TB) (QuantiFERON) at screening;

          9. No prior Bacillus Calmette-Guérin (BCG) exposure either through birth vaccinations
             (born in North American) or BCG bladder cancer treatment.

         10. Documentation of current flu season vaccination dated at least 60 days prior to
             baseline visit.

        Exclusion Criteria:

        Study subjects meeting any of the following criteria will not be allowed to enroll in the
        study:

          1. History of chronic infectious disease, such as HIV or untreated or active hepatitis;

          2. History of tuberculosis, positive interferon-gamma release assay (IGRA, also known as
             the QuantiFERON-TB test), including a test with a high reactivity to mycobacteria of
             non-tuberculosis variety;

          3. Prior BCG vaccination, positive T-spot tuberculosis test or a T-spot test showing
             significant Mycobacteria exposure;

          4. A positive Severe acute respiratory syndrome coronavirus, Polymerase Chain Reaction
             (PCR) result within 3 months of screening, or known close contact with a confirmed
             Coronavirus 19 (COVID-19) positive person or symptoms highly suspicious for COVID-19
             (per Center for Disease Control (CDC) guidelines) within 1 month of screening,
             including fever, cough, shortness of breath, chills, muscle pain, new loss of taste or
             smell, vomiting or diarrhea, and/or sore throat, based on clinician's judgment;

          5. History of treatment with metformin within the past one year;

          6. Previous participation (ever) in active immunization research for Alzheimer's Disease
             (AD) or passive immunotherapy or other disease-modifying treatments for AD within the
             past three months;

          7. Current treatment with immunosuppressants (calcineurin inhibitors, corticosteroids, or
             biological or cytotoxic immunosuppressants, or disease or condition likely to require
             high dose steroid or immunosuppressive therapy);

          8. Other conditions or treatments associated with increased risk of infections or
             treatment with immunosuppressive medications for any reason;

          9. Current treatment with aspirin > 160 mg/day or chronic, daily nonsteroidal
             anti-inflammatory drugs (NSAIDs);

         10. Chronic use of antibiotics;

         11. History of keloid formation;

         12. Living with someone who is immunosuppressed and/or at high risk for infectious
             diseases (for example, HIV+ or taking immunosuppressive medications for any reason),
             or in a job (e.g. healthcare) in which the subject works with immunosuppressed
             populations;

         13. Other/confounding neurological or psychiatric condition, unstable medical or
             psychiatric conditions, contraindications to BCG use and lab abnormalities or
             concurrent medication use posing risk for BCG or study procedures;

         14. Laboratory abnormalities in B12, Folate, thyroid stimulating hormone (TSH), or other
             common laboratory parameters that may contribute to cognitive dysfunction;

         15. Laboratory abnormalities in Complete Blood Count (CBC), electrolytes, Liver Function
             Tests (LFTs), Blood Urea Nitrogen (BUN), Creatinine (Cr), total serum immunoglobulins,
             erythrocyte sedimentation rate (ESR), C reactive protein (CRP), or urinalysis posing
             risk to treatment with BCG per clinician judgment;

         16. Laboratory abnormalities in prothrombin time /international normalized ratio (PT-INR),
             which would pose a risk to performing the lumbar puncture procedure;

         17. Discontinuation of cholinesterase inhibitor or memantine within one month (28 days)
             prior to baseline visit;

         18. Females who are pregnant, lactating or of child-bearing potential;

         19. If male with female partner(s) of childbearing potential, unwilling or unable to
             adhere to contraception requirements specified in the protocol.

         20. Administration of live vaccine <60 days prior to Baseline.

         21. Increased intracranial pressure as determined on a fundoscopy/neurological examination
             performed within 30 days of Lumbar Puncture (LP);

         22. COVID-19 vaccination < 60 days prior to baseline or within 14 days of BCG
             immunizations.