HealthyPhase 2NCT04507126

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

A Phase 2 study testing Bacillus Calmette-Guerin (BCG) in people with Healthy, run by Massachusetts General Hospital at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

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

Who is it for?: Ages 55 to 80 yearsHealthy volunteers can take part
Conditions the study is for: Healthy
What is being tested?: Bacillus Calmette-Guerin (BCG)
Type of treatment: Vaccines, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 20 participants
Where: 1 siteUnited States
Study dates: 1 Mar 2021to 9 Dec 2022
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 55 to 80 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

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;

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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.

Who cannot join

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;

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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;
Laboratory abnormalities in Complete Blood Count (CBC), electrolytes, Liver Function Tests (LFTs), Blood Urea Nitrogen (BUN), Creatinine (Cr), total serum immunoglobulins, erythrocyte sedimentation rate (ESR), C reactive protein (CRP), or urinalysis posing risk to treatment with BCG per clinician judgment;
Laboratory abnormalities in prothrombin time /international normalized ratio (PT-INR), which would pose a risk to performing the lumbar puncture procedure;
Discontinuation of cholinesterase inhibitor or memantine within one month (28 days) prior to baseline visit;
Females who are pregnant, lactating or of child-bearing potential;
If male with female partner(s) of childbearing potential, unwilling or unable to adhere to contraception requirements specified in the protocol.
Administration of live vaccine <60 days prior to Baseline.
Increased intracranial pressure as determined on a fundoscopy/neurological examination performed within 30 days of Lumbar Puncture (LP);
COVID-19 vaccination < 60 days prior to baseline or within 14 days of BCG immunizations.

Trial locations and contacts

1 site in 1 country.

United States1 site

Clinical Translational Research Unit
Charlestown, Massachusetts, 02124

Other trials in United States

About this study

Official title: Effects of Bacillus Calmette-Guérin (BCG) Immunization on Cerebrospinal Fluid (CSF) and Blood-Based Biomarkers in Older Adults: A Pilot

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

Read the 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.

Conditions: Healthy
Being tested: Bacillus Calmette-Guerin (BCG)
Keywords: Cognition, Alzheimer's disease, Memory, BCG, Immunization
Medical subject headings: Alzheimer Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Bacillus Calmette-Guerin (BCG)Biological
Vaccine

Study groups in NCT04507126
Study group	Role	What they receive
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. Receives: Biological: Bacillus Calmette-Guerin (BCG)

What is being measured

The primary outcome is the main question the study is designed to answer.

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)
Measured: 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
Measured: 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
Median difference of biomarkers measured in pg/mL (Amyloid-β42/40, phospho-tau (p181 tau), glial fibrillary astrocytic protein (GFAP) and neurofilament light protein (NFL) biomarkers) in CSF from baseline to 90 days.
Measured: Day 90 compared to Day 0
Median Fold Change in CSF Biomarkers of Pharmacodynamic Response From Day 0 to Day 90
Median Fold change in CSF biomarkers from baseline measured in pg/mL (Interleukin 6 (IL6), Tumor Necrosis Factor alpha (TNFa), interleukin 1 beta (IL1beta), Interferon gamma (IFNg))
Measured: Day 90 compared to Day 0
Cognitive Measures (RBANS) Total Scored Index, 3 Months After BCG Injection
Mean change in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) from baseline to 3 months after BCG injection. Total Scaled Index (TSI) . Higher scores mean better performance on the RBANS Total Scaled Index.
TSI Minimum 40, TSI Maximum 160.
Measured: Day 90 compared to Day 0
Median Fold Change in Circulating Cytokines From Day 0 to Day 90
Median Fold change in circulating cytokines in plasma from baseline measured in pg/mL (IL6, TNFa, IL1beta, IFNg)
Measured: Time Frame: Day 90 compared to Day 0

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Mar 20219 Dec 2022

First posted11 Aug 2020
Study start1 Mar 2021
Primary completion9 Dec 2022
Study completion9 Dec 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for HealthyStudies of the same condition, open and under way.
More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Other
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 20 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04507126
Sponsor's protocol ID: 2020P002042
Other IDs: 2021P001980
Status last verified: Oct 2025
First submitted: 23 Jun 2020
Last updated: 12 Dec 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

Weinberg MS, Kodali MC, Li Z, Galler JA, Tidball AR, Reynolds WC, Young C, Devitte-McKee K, Fatima HA, Kivisakk P, Chatterjee M, Kulkarni A, Billingsly JM, Bartlett AL, Sui SH, Kuhtreiber WM, Gerber J, McManus AJ, Tanzi RE, Das S, Faustman DL, Arnold SE. Bacillus Calmette-Guerin (BCG) immunotherapy reprograms CNS immunity and alters Alzheimer's biomarkers: results from two open-label clinical trials. Commun Med (Lond). 2026 Jul 2;6(1):358. doi: 10.1038/s43856-026-01691-7.
PubMed 42393277

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 12 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Effects of Bacillus Calmette-Guérin (BCG) Immunization on Cerebrospinal Fluid (CSF) and Blood-Based Biomarkers in Older Adults: A Pilot
ClinicalTrials.gov ID: NCT04507126
Acronym / sponsor ID: 2020P002042
Conditions: Healthy
Keywords: Cognition, Alzheimer's disease, Memory, BCG, Immunization
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 20 participants (actual)
Lead sponsor: Massachusetts General HospitalUniversity, hospital or other
Study start: 1 Mar 2021 (actual)
Primary completion: 9 Dec 2022 (actual)
Study completion: 9 Dec 2022 (actual)
First posted: 11 Aug 2020 (actual)
Results: Posted 3 Oct 2023

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Detailed description

Study design

Primary purpose: Other
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
BCG Immunization	Experimental	Biological: Bacillus Calmette-Guerin (BCG)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.

Who may qualify

Ages: 55 to 80 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (11 listed)

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;

Key exclusion criteria (23 listed)

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;

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Bacillus Calmette-Guerin (BCG)Vaccine	Biological	BCG Immunization

Primary outcome

Median Fold Change of Cytokine Levels From Day 0 to Day 90
Time frame: Day 90 compared to Day 0
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)
Number of Participants With Treatment-Related Adverse Events
Time frame: AEs were collected from baseline through study completion, an average of 390 days
Number of Participants With Treatment-Related Adverse Events to determine safety of BCG

4 secondary outcomes

Median Difference in CSF Biomarkers of Alzheimer's Disease (AD) Pathology From Day 0 to Day 90
Time frame: Day 90 compared to Day 0
Median Fold Change in CSF Biomarkers of Pharmacodynamic Response From Day 0 to Day 90
Time frame: Day 90 compared to Day 0
Cognitive Measures (RBANS) Total Scored Index, 3 Months After BCG Injection
Time frame: Day 90 compared to Day 0
Median Fold Change in Circulating Cytokines From Day 0 to Day 90
Time frame: Time Frame: Day 90 compared to Day 0

Results and safety

Results posted to the registry on 3 Oct 2023, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
BCG Immunization	20	13

Primary outcome: Median Fold Change of Cytokine Levels From Day 0 to Day 90

Time frame: Day 90 compared to Day 0. Median (95% Confidence Interval). Unit: pg/mL

Measure	BCG Immunization n = 10
Interferon-gamma cytokine	3254 (281.1 to 7169)
Interleukin-1 beta cytokine	1.997 (-5.641 to 15.08)
Interleukin 6 cytokine	16.83 (-319.8 to 717.5)
Tumor necrosis factor alpha cytokine	-33.89 (-529.3 to 1746)

Primary outcome: Number of Participants With Treatment-Related Adverse Events

Time frame: AEs were collected from baseline through study completion, an average of 390 days. Count of participants. Unit: Participants

Measure	BCG Immunization n = 16
Value	0

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse event data was collected from baseline to end of study, up to 396 days.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
BCG Immunization	0 of 16 (0%)	7 of 16 (43.8%)	0 of 16

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 12 Dec 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 42393277Weinberg MS, Kodali MC, Li Z, Galler JA, Tidball AR, Reynolds WC, Young C, Devitte-McKee K, Fatima HA, Kivisakk P, Chatterjee M, Kulkarni A, Billingsly JM, Bartlett AL, Sui SH, Kuhtreiber WM, Gerber J, McManus AJ, Tanzi RE, Das S, Faustman DL, Arnold SE. Bacillus Calmette-Guerin (BCG) immunotherapy reprograms CNS immunity and alters Alzheimer's biomarkers: results from two open-label clinical trials. Commun Med (Lond). 2026 Jul 2;6(1):358. doi: 10.1038/s43856-026-01691-7.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Steven E Arnold, MD principal investigator

Massachusetts General Hospital

Denise Faustman, MD, PhD principal investigator

Massachusetts General Hospital

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Bacillus Calmette-Guerin (BCG) in people with Healthy, run by Massachusetts General Hospital at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 3 Oct 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Median Fold Change of Cytokine Levels From Day 0 to Day 90 (time frame: Day 90 compared to Day 0). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04507126, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Dec 2025.