A Trial to Evaluate the Effects of BCG in Adults With MCI and Mild-to-Moderate AD
Study Details
Study Description
Brief Summary
A study of the effects of Bacillus Calmette-Guérin (BCG) immunization on cerebrospinal fluid and blood-based biomarkers in older with mild cognitive impairment and mild-to-moderate to Alzheimer's disease.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 2 |
Detailed Description
This single-site, open-label trial will investigate the effects of BCG vaccination on IIR and AD biofluid biomarkers, magnetic resonance imaging (MRI) biomarkers, and neurocognitive/behavioral functioning over a one year period in older adults with mild cognitive impairment (MCI) to mild-to-moderate dementia due to AD. This study will also gather data on tolerability and safety.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: BCG Active BCG immunization |
Biological: Biological/Vaccine: Bacillus Calmette-Guerin (BCG)
Two Bacillus Calmette-Guérin (Japan BCG) vaccine injections spaced four week apart. Each injection will have 0.36-3.9 x 10^6 colony forming units (CFU) reconstituted in 0.1 mL saline.
Other Names:
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Outcome Measures
Primary Outcome Measures
- Blood biomarkers of pharmacodynamic response- cytokines [Day 364]
Change in concentration of circulating cytokines in blood from baseline
- Blood biomarkers of pharmacodynamic response- cytokines [Day 84]
Change in concentration of circulating cytokines in blood from baseline
- CSF biomarkers of pharmacodynamic response- cytokines [Day 84]
Change in concentration of circulating cytokines in CSF from baseline
- CSF biomarkers of pharmacodynamic response- cytokines [Day 364]
Change in concentration of circulating cytokines in CSF from baseline
- Blood biomarkers of AD pathology-ATN [Day 364]
Change in concentration of ATN markers of AD pathophysiology (Amyloid-β42/40, phospho-tau, total tau and neurofilament light protein biomarkers) in blood from baseline
- CSF biomarkers of AD pathology-ATN [Day 364]
Change in concentration of ATN markers of AD pathophysiology (Amyloid-β42/40, phospho-tau, total tau and neurofilament light protein biomarkers) in CSF from baseline
- Blood biomarkers of AD pathology-ATN [Day 84]
Change in concentration of ATN markers of AD pathophysiology (Amyloid-β42/40, phospho-tau, total tau and neurofilament light protein biomarkers) in blood from baseline
- CSF biomarkers of AD pathology-ATN [Day 84]
Change in concentration of ATN markers of AD pathophysiology (Amyloid-β42/40, phospho-tau, total tau and neurofilament light protein biomarkers) in CSF from baseline
- Cognitive Measures (RBANS) [Day 84]
Change from baseline in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) score
- Cognitive Measures (RBANS) [Day 364]
Change from baseline in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) score
Eligibility Criteria
Criteria
Inclusion Criteria:
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Individuals between the ages of 55-85;
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MCI or moderate dementia due to AD as defined by the 2011 NIA-AA Workgroup recommendations;
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MoCA ≥ 8 at screening;
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Global CDR between 0.5-2 (inclusive) at screening;
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Amyloid and/or tau biomarkers indicative of AD pathology;
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Education level, English language skills and literacy indicates subject will be able to complete all assessments;
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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;
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Willing and able to complete all assessment and study procedures, including blood and lumbar punctures, and clinical assessments;
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If on cholinesterase inhibitor and/or memantine, doses are stable for 3 months prior to baseline;
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Negative test results for HIV antibody and Tuberculosis (QuantiFERON) at screening;
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No prior BCG exposure either through birth vaccinations (born in North American) or BCG bladder cancer treatment.
Exclusion Criteria:
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History of chronic infectious disease, such as HIV or untreated or active hepatitis;
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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;
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Prior BCG vaccination, positive T-spot tuberculosis test or a T-spot test showing significant Mycobacteria exposure;
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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;
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History of treatment with metformin within the past one year;
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Treatment with other investigational agents which, at the discretion of the investigator, interfere with safety and/or study outcomes;
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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);
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Other conditions or treatments associated with increased risk of infections or treatment with immunosuppressive medications for any reason;
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Current treatment with aspirin > 160 mg/day or chronic, daily NSAIDs;
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Current (as of time of study screening) or chronic use of antibiotics;
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History of keloid formation;
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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;
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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;
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Laboratory abnormalities in B12, Folate, TSH, or other common laboratory parameters that may contribute to cognitive dysfunction per clinician judgment;
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Laboratory abnormalities in CBC, electrolytes, LFTs, BUN, Cr, total serum immunoglobulins, ESR, CRP, or urinalysis posing risk to treatment with BCG per clinician judgment;
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Laboratory abnormalities in PT-INR, which would pose a risk to performing the lumbar puncture procedure;
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Discontinuation of cholinesterase inhibitor or memantine within one month (28 days) prior to baseline visit;
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Females who are pregnant, lactating or of child-bearing potential;
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If male with female partner(s) of childbearing potential, unwilling or unable to adhere to contraception requirements specified in the protocol.
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Administration of live vaccine within 30 days of screening visit or BCG immunizations
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Administration of non-live vaccine within 14 days of screening visit or BCG immunizations
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If participating in optional MRI: Existing contraindication to MRI per MGH Athinoula
- Martinos Center research guidelines
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Alzheimer's Clinical and Translational Research Unit | Charlestown | Massachusetts | United States | 02129 |
Sponsors and Collaborators
- Steven E Arnold
Investigators
- Principal Investigator: Steven Arnold, MD, Massachusetts General Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2021P002577