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

• ClinicalTrials.gov Identifier: NCT05004688
• Recruitment Status: Recruiting
• First Posted: August 13, 2021
• Last Update Posted: July 12, 2022
• Sponsor: Steven E Arnold
• Information provided by (Responsible Party): Steven E Arnold, Massachusetts General Hospital

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
Mild Cognitive Impairment; Mild Dementia; Moderate Dementia; Alzheimer Disease	Biological: Biological/Vaccine: Bacillus Calmette-Guerin (BCG)	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

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 15 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: open-label
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: An Open-label Trial to Evaluate the Effects of BCG Immunization on Biomarkers of Inflammation/Immune Response and Alzheimer's Disease in Adults With Mild Cognitive Impairment and Mild-to-Moderate Dementia Due to Alzheimer's Disease
• Actual Study Start Date: March 25, 2022
• Estimated Primary Completion Date: October 1, 2023
• Estimated Study Completion Date: October 1, 2023

Arms and Interventions

Arm	Intervention/treatment
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 Name: BCG

Outcome Measures

Primary Outcome Measures :

1. Blood biomarkers of pharmacodynamic response- cytokines [ Time Frame: Day 364 ]
   Change in concentration of circulating cytokines in blood from baseline
2. Blood biomarkers of pharmacodynamic response- cytokines [ Time Frame: Day 84 ]
   Change in concentration of circulating cytokines in blood from baseline
3. CSF biomarkers of pharmacodynamic response- cytokines [ Time Frame: Day 84 ]
   Change in concentration of circulating cytokines in CSF from baseline
4. CSF biomarkers of pharmacodynamic response- cytokines [ Time Frame: Day 364 ]
   Change in concentration of circulating cytokines in CSF from baseline
5. Blood biomarkers of AD pathology-ATN [ Time Frame: 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
6. CSF biomarkers of AD pathology-ATN [ Time Frame: 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
7. Blood biomarkers of AD pathology-ATN [ Time Frame: 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
8. CSF biomarkers of AD pathology-ATN [ Time Frame: 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
9. Cognitive Measures (RBANS) [ Time Frame: Day 84 ]
   Change from baseline in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) score
10. Cognitive Measures (RBANS) [ Time Frame: Day 364 ]
    Change from baseline in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) score

Eligibility Criteria

• Ages Eligible for Study: 55 Years to 85 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Individuals between the ages of 55-85;
2. MCI or moderate dementia due to AD as defined by the 2011 NIA-AA Workgroup recommendations;
3. MoCA ≥ 8 at screening;
4. Global CDR between 0.5-2 (inclusive) at screening;
5. Amyloid and/or tau biomarkers indicative of AD pathology;
6. Education level, English language skills and literacy indicates subject will be able to complete all assessments;
7. 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;
8. Willing and able to complete all assessment and study procedures, including blood and lumbar punctures, and clinical assessments;
9. If on cholinesterase inhibitor and/or memantine, doses are stable for 3 months prior to baseline;
10. Negative test results for HIV antibody and Tuberculosis (QuantiFERON) at screening;
11. No prior BCG exposure either through birth vaccinations (born in North American) or BCG bladder cancer treatment.

Exclusion Criteria:

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 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;
5. History of treatment with metformin within the past one year;
6. Treatment with other investigational agents which, at the discretion of the investigator, interfere with safety and/or study outcomes;
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 NSAIDs;
10. Current (as of time of study screening) or 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, TSH, or other common laboratory parameters that may contribute to cognitive dysfunction per clinician judgment;
15. Laboratory abnormalities in CBC, electrolytes, LFTs, BUN, Cr, total serum immunoglobulins, ESR, CRP, or urinalysis posing risk to treatment with BCG per clinician judgment;
16. Laboratory abnormalities in 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 within 30 days of screening visit or BCG immunizations
21. Administration of non-live vaccine within 14 days of screening visit or BCG immunizations
22. If participating in optional MRI: Existing contraindication to MRI per MGH Athinoula A. Martinos Center research guidelines

Contacts and Locations

Contacts

Contact: Study Coordinator; 617-643-2351; ACTRUstudies@mgh.harvard.edu

Contact: Project Manager; 617-724-2463; mmriley@mgh.harvard.edu

Locations

United States, Massachusetts

Alzheimer's Clinical and Translational Research Unit; Recruiting

Charlestown, Massachusetts, United States, 02129

Contact: Kate Cropp

Principal Investigator: Steven Arnold, MD

Sponsors and Collaborators

Steven E Arnold

Investigators

• Principal Investigator: Steven Arnold, MD; Massachusetts General Hospital

More Information

• Responsible Party: Steven E Arnold, Professor of Neurology, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT05004688
• Other Study ID Numbers: 2021P002577
• First Posted: August 13, 2021
• Last Update Posted: July 12, 2022
• Last Verified: July 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Alzheimer Disease; Dementia; Cognitive Dysfunction; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Cognition Disorders; BCG Vaccine; Adjuvants, Immunologic; Immunologic Factors; Physiological Effects of Drugs