A Trial to Evaluate the Effects of BCG in Adults With MCI and Mild-to-Moderate AD

Prior treatment

• Prior BCG vaccination, positive T-spot tuberculosis test or a T-spot test showing significant Mycobacteria exposure;
• History of treatment with metformin within the past one year;
• Treatment with other investigational agents which, at the discretion of the investigator, interfere with safety and/or study outcomes;
• 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);
• Other conditions or treatments associated with increased risk of infections or treatment with immunosuppressive medications for any reason;
• Current treatment with aspirin \> 160 mg/day or chronic, daily NSAIDs;
• 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;
• Discontinuation of cholinesterase inhibitor or memantine within one month (28 days) prior to baseline visit;
• Administration of live vaccine within 30 days of screening visit or BCG immunizations
• Administration of non-live vaccine within 14 days of screening visit or BCG immunizations

Other illness

• History of chronic infectious disease, such as HIV or untreated or active hepatitis;
• 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;
• A positive SARS-CoV-2 PCR result within 3 months of screening, or known close contact with a confirmed COVID-19 positive person or symptoms highly suspicious for COVID-19 (per 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;
• History of keloid formation;
• 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;

Lab values

• Laboratory abnormalities in B12, Folate, TSH, or other common laboratory parameters that may contribute to cognitive dysfunction per clinician judgment;
• Laboratory abnormalities in CBC, electrolytes, LFTs, BUN, Cr, total serum immunoglobulins, ESR, CRP, or urinalysis posing risk to treatment with BCG per clinician judgment;
• Laboratory abnormalities in PT-INR, which would pose a risk to performing the lumbar puncture procedure;

Other

• Current (as of time of study screening) or chronic use of antibiotics;
• Females who are pregnant, lactating or of child-bearing potential;
• If male with female partner(s) of childbearing potential, unwilling or unable to adhere to contraception requirements specified in the protocol.
• If participating in optional MRI: Existing contraindication to MRI per MGH Athinoula A. Martinos Center research guidelines

• Individuals between the ages of 55-85;
• MCI or moderate dementia due to AD as defined by the 2011 NIA-AA Workgroup recommendations;
• MoCA ≥ 8 at screening;
• Global CDR between 0.5-2 (inclusive) at screening;
• Amyloid and/or tau biomarkers indicative of AD pathology;
• Education level, English language skills and literacy indicates subject will be able to complete all assessments;
• Has a study partner who, in the investigator's judgement, has frequent, direct contact with the participant at least several days a week, can accompany the participant to all visits, and is also able to provide information to study investigator/staff;
• Willing and able to complete all assessment and study procedures, including blood and lumbar punctures, and clinical assessments;
• If on cholinesterase inhibitor and/or memantine, doses are stable for 3 months prior to baseline;
• Negative test results for HIV antibody and Tuberculosis (QuantiFERON) at screening;
• No prior BCG exposure either through birth vaccinations (born in North American) or BCG bladder cancer treatment.