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Brief Title: A Pilot Study of the Effects of Bacillus Calmette-Guérin (BCG) Immunization on Cerebrospinal Fluid and Blood-based Biomarkers in Older Adults.

Effects of BCG Immunization on Cerebrospinal Fluid and Blood-Based Biomarkers in Older Adults: A Pilot

INTRODUCTION

  • Org Study ID: 2020P002042
  • Secondary ID: N/A
  • NCT ID: NCT04507126
  • Sponsor: Massachusetts General Hospital

BRIEF SUMMARY


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

DETAILED DESCRIPTION


This single-site, open-label clinical trial will investigate the immune and neurobiological
effects of BCG vaccination in cognitively unimpaired older adults and older adults with
memory and thinking problems by measuring target engagement, pharmacodynamic response, and
effect on Alzheimer's disease (AD) pathology and immune response markers. This study will
also gather data on study feasibility, tolerability, and safety.


  • Overall Status
    Recruiting
  • Start Date
    March 1, 2021
  • Phase
    Early Phase 1
  • Study Type
    Interventional

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: CSF biomarkers of pharmacodynamic response- cytokines

Primary Outcome 1 - Timeframe: Day 84

Primary Outcome 2 - Measure: CSF biomarkers of AD pathology-ATN

Primary Outcome 2 - Timeframe: Day 84

Primary Outcome 3 - Measure: Blood biomarkers of pharmacodynamic response- cytokines

Primary Outcome 3 - Timeframe: Day 28

Primary Outcome 4 - Measure: Blood biomarkers of pharmacodynamic response- cytokines

Primary Outcome 4 - Timeframe: Day 84

Primary Outcome 5 - Measure: Blood biomarkers of AD pathology

Primary Outcome 5 - Timeframe: Day 28

Primary Outcome 6 - Measure: Blood biomarkers of AD pathology

Primary Outcome 6 - Timeframe: Day 84

CONDITION

  • Mild Cognitive Impairment
  • Healthy

ELIGIBILITY


Inclusion Criteria:

Study subjects meeting all the following criteria will be allowed to enroll in the study:

1. Age 55-80 inclusive;

2. MoCA ≥18;

3. Normal cognition as defined by MoCA ≥ 26 or MCI as defined by the 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 HIV antibody and Tuberculosis (QuantiFERON) at screening;

9. No prior 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 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. Previous participation (ever) in active immunization research for 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 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, TSH, or other common laboratory parameters
that may contribute to cognitive dysfunction;

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 <60 days prior to Baseline.

21. Increased intracranial pressure as determined on a fundoscopy/neurological examination
performed within 30 days of LP;

22. COVID-19 vaccination < 60 days prior to baseline or within 14 days of BCG
immunizations.

Gender: All

Minimum Age: 80 Years

Maximum Age: 55 Years

Healthy Volunteers: Accepts Healthy Volunteers

OFFICIAL INFORMATION

Name: Steven E Arnold, MD

Role: Principal Investigator

Affiliation: Massachusetts General Hospital

Overall Contact

Name: Steven E Arnold, MD

Phone: 617-643-2351

Email: ACTRUstudies@mgh.harvard.edu

LOCATION

Facility Status Contact
Facility: Clinical Translational Research Unit
Charlestown, Massachusetts 02124
United States 		Status: Recruiting Contact: Jessica Gerber
617-724-1992
jgerber2@mgh.harvard.edu

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