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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05004688
Recruitment Status : Recruiting
First Posted : August 13, 2021
Last Update Posted : July 12, 2022
Sponsor:
Information provided by (Responsible Party):
Steven E Arnold, Massachusetts General Hospital

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.

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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


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




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



Information from the National Library of Medicine

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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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05004688


Contacts
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Contact: Study Coordinator 617-643-2351 ACTRUstudies@mgh.harvard.edu
Contact: Project Manager 617-724-2463 mmriley@mgh.harvard.edu

Locations
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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
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Principal Investigator: Steven Arnold, MD Massachusetts General Hospital
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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    Key Record Dates
Last Update Posted: July 12, 2022
Last Verified: July 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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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