A Pilot Study of the Effects of BCG Immunization on CSF and Blood-based Biomarkers in Older Adults.

NCT04507126 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 2020P0020422021P001980
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Healthy

Keywords

Cognition; Alzheimer's disease; Memory; BCG; Immunization

Outcome Measures

Primary Outcomes (2)

• Median Fold Change of Cytokine Levels From Day 0 to Day 90

  Heat-killed BCG or Lipopolysaccharide (LPS) applied to peripheral blood mononuclear cells (PBMCs) from subjects at 0 and 90d after study start. Calculated as median fold change of cytokine levels in media at day 90 (pg/mL) compared to day 0 (pg/mL)

  Day 90 compared to Day 0

• Number of Participants With Treatment-Related Adverse Events

  Number of Participants With Treatment-Related Adverse Events to determine safety of BCG

  AEs were collected from baseline through study completion, an average of 390 days

Secondary Outcomes (4)

• Median Difference in CSF Biomarkers of Alzheimer's Disease (AD) Pathology From Day 0 to Day 90

  Day 90 compared to Day 0

• Median Fold Change in CSF Biomarkers of Pharmacodynamic Response From Day 0 to Day 90

  Day 90 compared to Day 0

• Cognitive Measures (RBANS) Total Scored Index, 3 Months After BCG Injection

  Day 90 compared to Day 0

• Median Fold Change in Circulating Cytokines From Day 0 to Day 90

  Time Frame: Day 90 compared to Day 0

Study Arms (1)

BCG Immunization

EXPERIMENTAL

All participants will receive two Bacillus Calmette-Guérin (Japan BCG) vaccine injections spaced four week apart. Each injection will have 1.8-3.9 x 10\^6 colony forming units (CFU) reconstituted in 0.1 mL saline.

Biological: Bacillus Calmette-Guerin (BCG)

Interventions

Bacillus Calmette-Guerin (BCG) BIOLOGICAL

Vaccine

BCG Immunization

Eligibility Criteria

• Age: 55 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Study subjects meeting all the following criteria will be allowed to enroll in the study:
• Age 55-80 inclusive;
• Montreal Cognitive Assessment (MoCA ) ≥18;
• Normal cognition as defined by Montreal Cognitive Assessment (MoCA) ≥ 26 or Mild Cognitive Impairment (MCI) as defined by the National Institute of Health Alzheimer's Association (NIA-AA) Workgroup (2011) and MoCA score between 18 and 25 (inclusive);
• Education level, English language skills, and literacy indicates subject will be able to complete all assessments;
• Ability to provide informed consent;
• Willing and able to complete all assessment and study procedures, including blood draws, 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 Human Immunodeficiency Virus (HIV) antibody and Tuberculosis (TB) (QuantiFERON) at screening;
• No prior Bacillus Calmette-Guérin (BCG) exposure either through birth vaccinations (born in North American) or BCG bladder cancer treatment.
• Documentation of current flu season vaccination dated at least 60 days prior to baseline visit.

You may not qualify if:

• Study subjects meeting any of the following criteria will not be allowed to enroll in the study:
• 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;
• Prior BCG vaccination, positive T-spot tuberculosis test or a T-spot test showing significant Mycobacteria exposure;
• A positive Severe acute respiratory syndrome coronavirus, Polymerase Chain Reaction (PCR) result within 3 months of screening, or known close contact with a confirmed Coronavirus 19 (COVID-19) positive person or symptoms highly suspicious for COVID-19 (per Center for Disease Control (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 treatment with metformin within the past one year;
• Previous participation (ever) in active immunization research for Alzheimer's Disease (AD) or passive immunotherapy or other disease-modifying treatments for AD within the past three months;
• 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 nonsteroidal anti-inflammatory drugs (NSAIDs);
• Chronic use of antibiotics;
• 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;
• 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;
• Laboratory abnormalities in B12, Folate, thyroid stimulating hormone (TSH), or other common laboratory parameters that may contribute to cognitive dysfunction;

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Clinical Translational Research Unit

Charlestown, Massachusetts, 02124, United States

Location

MeSH Terms

Conditions

Alzheimer Disease

Interventions

BCG Vaccine

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Tuberculosis Vaccines; Bacterial Vaccines; Vaccines; Biological Products; Complex Mixtures

Results Point of Contact

• Title: Research Operations Director
• Organization: MGH

jgerber2@mgh.harvard.edu

617-724-1992

Study Officials

• Steven E Arnold, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

• Denise Faustman, MD, PhD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Neurology

Study Record Dates

• First Submitted: June 23, 2020
• First Posted: August 11, 2020
• Study Start: March 1, 2021
• Primary Completion: December 9, 2022
• Study Completion: December 9, 2022
• Last Updated: December 12, 2025
• Results First Posted: October 3, 2023

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)