Mild Cognitive ImpairmentPhase 2NCT05004688

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

A Phase 2 study testing Biological/Vaccine: Bacillus Calmette-Guerin (BCG) in people with Mild Cognitive Impairment and Mild Dementia, run by Steven E Arnold, MD 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

Search all trials

Trial 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. Read more about this study

Who is it for?: Ages 55 to 85 years
Conditions the study is for: Mild Cognitive Impairment, Mild Dementia, Moderate Dementia
What is being tested?: Biological/Vaccine: 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: 15 participants
Where: 1 siteUnited States
Study dates: 25 Mar 2022to 15 Jan 2024
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 85 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Individuals between the ages of 55-85;
MCI or moderate dementia due to AD as defined by the 2011 NIA-AA Workgroup recommendations;
MoCA ≥ 8 at screening;
Global CDR between 0.5-2 (inclusive) at screening;
Amyloid and/or tau biomarkers indicative of AD pathology;
Education level, English language skills and literacy indicates subject will be able to complete all assessments;

Show all 11Show fewer

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;
Willing and able to complete all assessment and study procedures, including blood and 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 HIV antibody and Tuberculosis (QuantiFERON) at screening;
No prior BCG exposure either through birth vaccinations (born in North American) or BCG bladder cancer treatment.

Who cannot join

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 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;
History of treatment with metformin within the past one year;
Treatment with other investigational agents which, at the discretion of the investigator, interfere with safety and/or study outcomes;

Show all 22Show fewer

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 NSAIDs;
Current (as of time of study screening) or 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, TSH, or other common laboratory parameters that may contribute to cognitive dysfunction per clinician judgment;
Laboratory abnormalities in CBC, electrolytes, LFTs, BUN, Cr, total serum immunoglobulins, ESR, CRP, or urinalysis posing risk to treatment with BCG per clinician judgment;
Laboratory abnormalities in 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 within 30 days of screening visit or BCG immunizations
Administration of non-live vaccine within 14 days of screening visit or BCG immunizations
If participating in optional MRI: Existing contraindication to MRI per MGH Athinoula A. Martinos Center research guidelines

Trial locations and contacts

1 site in 1 country.

United States1 site

Alzheimer's Clinical and Translational Research Unit
Charlestown, Massachusetts, 02129

Other trials in United States

About this study

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

Read the 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.

Conditions: Mild Cognitive Impairment, Mild Dementia, Moderate Dementia, Alzheimer Disease
Being tested: Biological/Vaccine: Bacillus Calmette-Guerin (BCG)
Medical subject headings: Cognitive Dysfunction, Alzheimer Disease

What participants receive

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

Biological/Vaccine: Bacillus Calmette-Guerin (BCG)Biological
Also called 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.

Study groups in NCT05004688
Study group	Role	What they receive
BCG	Experimental	Active BCG immunization Receives: Biological: Biological/Vaccine: Bacillus Calmette-Guerin (BCG)

What is being measured

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

Blood Biomarkers of Pharmacodynamic Response- Cytokines
Change in concentration (Average difference) of circulating cytokines in blood from baseline (Average difference).Cytokines include: Plasma IFN-g (pg/ml), Plasma IL-1b (pg/ml), Plasma IL-2 (pg/ml), Plasma IL-6 (pg/ml), Plasma IL-10 (pg/ml), Plasma TNF-a (pg/ml).
Mean differences (and standard deviations) from baseline values are presented for the Day 364 (end of study) sample collections for the 4 participants in the study.
Measured: Baseline to Day 364
CSF Biomarkers of Pharmacodynamic Response- Cytokines
Change in concentration (Average difference) of circulating cytokines in CSF from baseline (Average difference). Cytokines measured include: CSF IFN-g (pg/ml), CSF IL-1b (pg/ml), CSF IL-2 (pg/ml), CSF IL-6 (pg/ml), CSF IL-10 (pg/ml), CSF TNF-a (pg/ml).
Mean differences (and standard deviations) from baseline values are presented for the Day 84 sample collections for the 7 participants with complete data in the study.
Measured: Baseline to Day 84
CSF Biomarkers of Pharmacodynamic Response- Cytokines
Change in concentration (Average Difference) of circulating cytokines in CSF from baseline. Cytokines measured include: CSF IFN-g (pg/ml), CSF IL-1b (pg/ml), CSF IL-2 (pg/ml), CSF IL-6 (pg/ml), CSF IL-10 (pg/ml), CSF TNF-a (pg/ml).
Mean differences (and standard deviations) from baseline values are presented for the Day 364 (end of study) sample collections for the 4 participants with complete data in the study.
Measured: Baseline to Day 364
Blood Biomarkers of AD Pathology-ATN
Change in concentration (Average difference) of ATN markers of AD pathophysiology phospho-tau (217 and 181) and neurofilament light protein biomarkers in blood from baseline.
Mean differences (and standard deviations) from baseline values are presented for the Day 364 (end of study) sample collections for the 4 participants in the study at this timepoint.
Measured: Baseline to Day 364
CSF Biomarkers of AD Pathology-ATN
Change in concentration (Average difference) of ATN markers of AD pathophysiology (phospho-tau181, total tau, and neurofilament light protein biomarkers in CSF from baseline.
Mean differences (and standard deviations) from baseline values are presented Day 364 (end of study) sample collections for the 4 participants in the study at this timepoint.
Measured: Baseline to Day 364
Blood Biomarkers of AD Pathology-ATN
Change in concentration (Average difference) of ATN markers of AD pathophysiology (phospho-tau (217 and 181) and neurofilament light protein biomarkers in blood from baseline.
Mean differences (and standard deviations) from baseline values are presented for the Day 84 sample collections for the 7 participants in the study at this timepoint.
Measured: Baseline to Day 84
CSF Biomarkers of AD Pathology-ATN
Change in concentration (Average difference) of ATN markers of AD pathophysiology (phospho-tau181, total tau, and neurofilament light protein biomarkers in CSF from baseline.
Mean differences (and standard deviations) from baseline values are presented for the Day 84 sample collections for the 4 participants in the study at this timepoint.
Measured: Baseline to Day 84
Cognitive Measures (RBANS)
Change in Total Scale Index (TSI) of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Mean differences and standard deviations are expressed for the difference between the Day 84 TSI and the baseline TSI for the 7 participants in the study.
The RBANS is an assessment commonly used in clinical trials to assess cognitive functioning. Scores range from 40 to 160 with lower scores indicating poorer performance, thus a score decrease would indicate a decrease in cognitive performance. A score under 78 is typically indicative of cognitive impairment.
Measured: Baseline to Day 84
Cognitive Measures (RBANS)
Change in Total Scale Index (TSI) of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Mean differences and standard deviations are expressed for the difference between the end of study TSI and the baseline TSI for the 4 participants in the study.
The RBANS is an assessment commonly used in clinical trials to assess cognitive functioning. Scores range from 40 to 160 with lower scores indicating poorer performance, thus a score decrease would indicate a decrease in cognitive performance. A score under 78 is typically indicative of cognitive impairment.
Measured: Baseline to Day 364
Amyloid-β42/40 Average Difference in Blood
Average difference of ATN markers of AD pathophysiology (Amyloid-β42/40 ratio) in blood from baseline.
Measured: Baseline to Day 364
Amyloid-β42/40 Average Difference in CSF
Average difference of ATN markers of AD pathophysiology (Amyloid-β42/40) in CSF from baseline.
Measured: Baseline to Day 364
Amyloid-β42/40 Average Difference in Blood - Baseline to Day 84
Average difference of ATN markers of AD pathophysiology (Amyloid-β42/40) in blood from baseline.
Measured: Baseline to Day 84
Amyloid-β42/40 Average Difference in CSF - Baseline to Day 84
Average difference of ATN markers of AD pathophysiology (Amyloid-β42/40) in CSF from baseline.
Measured: Baseline to Day 84
Blood Biomarkers of Pharmacodynamic Response - Cytokines
Change in concentration of circulating cytokines in blood plasma from baseline. Cytokines include: Plasma IFN-g (pg/ml), Plasma IL-1b (pg/ml), Plasma IL-2 (pg/ml), Plasma IL-6 (pg/ml), Plasma IL-10 (pg/ml), Plasma TNF-a (pg/ml). Mean differences (and standard deviations) from baseline values are presented for the Day 84 sample collections for the 7 participants in the study at that time.
Measured: Baseline to Day 84

Timeline

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

25 Mar 202215 Jan 2024

First posted13 Aug 2021
Study start25 Mar 2022
Primary completion15 Jan 2024
Study completion15 Jan 2024

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 Mild Cognitive ImpairmentStudies of the same condition, open and under way.
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
Model description: open-label
Masking: None (open label)
Enrolment: 15 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05004688
Sponsor's protocol ID: 2021P002577
Status last verified: Mar 2025
First submitted: 6 Aug 2021
Last updated: 13 Apr 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

RecruitingPhase 1
PET Imaging of Phosphodiesterase-4 (PDE4) in Volunteers With Alzheimer Disease (AD) or Mild Cognitive Impairment (MCI)
Alzheimer s Disease, Mild Cognitive Impairment
RecruitingObservational study
Community-based Screening for Alzheimer's Disease
Alzheimer's Disease(AD), Mild Cognitive Impairment (MCI)
RecruitingObservational study
InRAD Observational Study
Alzheimer's Disease(AD), Mild Cognitive Impairment (MCI)
Recruiting
Treating Insomnia in Mild Cognitive Impairment
Mild Cognitive Impairment (MCI), Insomnia
Recruiting
Telehealth-Adapted Compensatory Training and Intervention for Cognition
MCI, Mild Cognitive Impairment

All Mild Cognitive Impairment trials

Study at a glance

From the registry record, last updated by the sponsor on 13 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT05004688
Acronym / sponsor ID: 2021P002577
Conditions: Mild Cognitive Impairment, Mild Dementia, Moderate Dementia, Alzheimer Disease
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 15 participants (actual)
Lead sponsor: Steven E Arnold, MDUniversity, hospital or other
Study start: 25 Mar 2022 (actual)
Primary completion: 15 Jan 2024 (actual)
Study completion: 15 Jan 2024 (actual)
First posted: 13 Aug 2021 (actual)
Results: Posted 13 Apr 2025

Clinical summary

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

Detailed description

Study design

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

Arm	Type	Receives
BCG	Experimental	Biological: Biological/Vaccine: Bacillus Calmette-Guerin (BCG)Active BCG immunization

Who may qualify

Ages: 55 to 85 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (11 listed)

Individuals between the ages of 55-85;
MCI or moderate dementia due to AD as defined by the 2011 NIA-AA Workgroup recommendations;
MoCA ≥ 8 at screening;
Global CDR between 0.5-2 (inclusive) at screening;
Amyloid and/or tau biomarkers indicative of AD pathology;

Key exclusion criteria (22 listed)

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 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;
History of treatment with metformin within the past one year;

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
Biological/Vaccine: Bacillus Calmette-Guerin (BCG)Also: BCGTwo 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.	Biological	BCG

Primary outcome

Blood Biomarkers of Pharmacodynamic Response- Cytokines
Time frame: Baseline to Day 364
Change in concentration (Average difference) of circulating cytokines in blood from baseline (Average difference).Cytokines include: Plasma IFN-g (pg/ml), Plasma IL-1b (pg/ml), Plasma IL-2 (pg/ml), Plasma IL-6 (pg/ml), Plasma IL-10 (pg/ml), Plasma TNF-a (pg/ml). Mean differences (and standard deviations) from baseline values are presented for the Day 364 (end of study) sample collections for the 4 participants in the study.
CSF Biomarkers of Pharmacodynamic Response- Cytokines
Time frame: Baseline to Day 84
Change in concentration (Average difference) of circulating cytokines in CSF from baseline (Average difference). Cytokines measured include: CSF IFN-g (pg/ml), CSF IL-1b (pg/ml), CSF IL-2 (pg/ml), CSF IL-6 (pg/ml), CSF IL-10 (pg/ml), CSF TNF-a (pg/ml). Mean differences (and standard deviations) from baseline values are presented for the Day 84 sample collections for the 7 participants with complete data in the study.
CSF Biomarkers of Pharmacodynamic Response- Cytokines
Time frame: Baseline to Day 364
Change in concentration (Average Difference) of circulating cytokines in CSF from baseline. Cytokines measured include: CSF IFN-g (pg/ml), CSF IL-1b (pg/ml), CSF IL-2 (pg/ml), CSF IL-6 (pg/ml), CSF IL-10 (pg/ml), CSF TNF-a (pg/ml). Mean differences (and standard deviations) from baseline values are presented for the Day 364 (end of study) sample collections for the 4 participants with complete data in the study.
Blood Biomarkers of AD Pathology-ATN
Time frame: Baseline to Day 364
Change in concentration (Average difference) of ATN markers of AD pathophysiology phospho-tau (217 and 181) and neurofilament light protein biomarkers in blood from baseline. Mean differences (and standard deviations) from baseline values are presented for the Day 364 (end of study) sample collections for the 4 participants in the study at this timepoint.
CSF Biomarkers of AD Pathology-ATN
Time frame: Baseline to Day 364
Change in concentration (Average difference) of ATN markers of AD pathophysiology (phospho-tau181, total tau, and neurofilament light protein biomarkers in CSF from baseline. Mean differences (and standard deviations) from baseline values are presented Day 364 (end of study) sample collections for the 4 participants in the study at this timepoint.
Blood Biomarkers of AD Pathology-ATN
Time frame: Baseline to Day 84
Change in concentration (Average difference) of ATN markers of AD pathophysiology (phospho-tau (217 and 181) and neurofilament light protein biomarkers in blood from baseline. Mean differences (and standard deviations) from baseline values are presented for the Day 84 sample collections for the 7 participants in the study at this timepoint.
CSF Biomarkers of AD Pathology-ATN
Time frame: Baseline to Day 84
Change in concentration (Average difference) of ATN markers of AD pathophysiology (phospho-tau181, total tau, and neurofilament light protein biomarkers in CSF from baseline. Mean differences (and standard deviations) from baseline values are presented for the Day 84 sample collections for the 4 participants in the study at this timepoint.
Cognitive Measures (RBANS)
Time frame: Baseline to Day 84
Change in Total Scale Index (TSI) of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Mean differences and standard deviations are expressed for the difference between the Day 84 TSI and the baseline TSI for the 7 participants in the study. The RBANS is an assessment commonly used in clinical trials to assess cognitive functioning. Scores range from 40 to 160 with lower scores indicating poorer performance, thus a score decrease would indicate a decrease in cognitive performance. A score under 78 is typically indicative of cognitive impairment.
Cognitive Measures (RBANS)
Time frame: Baseline to Day 364
Change in Total Scale Index (TSI) of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Mean differences and standard deviations are expressed for the difference between the end of study TSI and the baseline TSI for the 4 participants in the study. The RBANS is an assessment commonly used in clinical trials to assess cognitive functioning. Scores range from 40 to 160 with lower scores indicating poorer performance, thus a score decrease would indicate a decrease in cognitive performance. A score under 78 is typically indicative of cognitive impairment.
Amyloid-β42/40 Average Difference in Blood
Time frame: Baseline to Day 364
Average difference of ATN markers of AD pathophysiology (Amyloid-β42/40 ratio) in blood from baseline.
Amyloid-β42/40 Average Difference in CSF
Time frame: Baseline to Day 364
Average difference of ATN markers of AD pathophysiology (Amyloid-β42/40) in CSF from baseline.
Amyloid-β42/40 Average Difference in Blood - Baseline to Day 84
Time frame: Baseline to Day 84
Average difference of ATN markers of AD pathophysiology (Amyloid-β42/40) in blood from baseline.
Amyloid-β42/40 Average Difference in CSF - Baseline to Day 84
Time frame: Baseline to Day 84
Average difference of ATN markers of AD pathophysiology (Amyloid-β42/40) in CSF from baseline.
Blood Biomarkers of Pharmacodynamic Response - Cytokines
Time frame: Baseline to Day 84
Change in concentration of circulating cytokines in blood plasma from baseline. Cytokines include: Plasma IFN-g (pg/ml), Plasma IL-1b (pg/ml), Plasma IL-2 (pg/ml), Plasma IL-6 (pg/ml), Plasma IL-10 (pg/ml), Plasma TNF-a (pg/ml). Mean differences (and standard deviations) from baseline values are presented for the Day 84 sample collections for the 7 participants in the study at that time.

Results and safety

Results posted to the registry on 13 Apr 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Active BCG Immunization	15	4

Primary outcome: Blood Biomarkers of Pharmacodynamic Response- Cytokines

Time frame: Baseline to Day 364. Mean (Standard Deviation). Unit: picogram/milliliter (pg/ml)

Measure	Active BCG Immunization n = 4
Plasma IFN-g (pg/ml)	26.672 (125.864)
Plasma IL-1b (pg/ml)	190.829 (181.329)
Plasma IL-2 (pg/ml)	20.309 (19.205)
Plasma IL-6 (pg/ml)	2293.879 (4308.539)
Plasma IL-10 (pg/ml)	366.090 (656.157)
Plasma TNF-a (pg/ml)	53.903 (54.002)

Primary outcome: CSF Biomarkers of Pharmacodynamic Response- Cytokines

Time frame: Baseline to Day 84. Mean (Standard Deviation). Unit: picogram/milliliter (pg/ml)

Measure	Active BCG Immunization n = 7
CSF IFN-g (pg/ml)	0.053 (13.002)
CSF IL-1b (pg/ml)	-1.287 (15.192)
CSF IL-2 (pg/ml)	8.103 (20.326)
CSF IL-6 (pg/ml)	21.009 (1220.991)
CSF IL-10 (pg/ml)	-3.057 (80.133)
CSF TNF-a (pg/ml)	-0.396 (11.426)

Population analysed: Since this outcome was analyzing the average difference between Day 0 and Day 84, there were more participants enrolled for these times points than when comparing Day 0 to Day 364. 15 participants started the trial, and only 4 completed, thus there were 7 active participants for the Day 84 timepoint.

Primary outcome: CSF Biomarkers of Pharmacodynamic Response- Cytokines

Time frame: Baseline to Day 364. Mean (Standard Deviation). Unit: picogram/milliliter (pg/ml)

Measure	Active BCG Immunization n = 4
CSF IFN-g (pg/ml)	-14.368 (13.773)
CSF IL-1b (pg/ml)	5.510 (10.867)
CSF IL-2 (pg/ml)	-12.910 (22.841)
CSF IL-6 (pg/ml)	710.455 (1827.730)
CSF IL-10 (pg/ml)	-95.078 (144.162)
CSF TNF-a (pg/ml)	0.300 (19.083)

Primary outcome: Blood Biomarkers of AD Pathology-ATN

Time frame: Baseline to Day 364. Mean (Standard Deviation). Unit: picogram/milliliter (pg/ml)

Measure	Active BCG Immunization n = 4
Plasma pTau217 (pg/ml)	-1.392 (5.382)
Plasma pTau181 (pg/ml)	0.233 (0.362)
Plasma NfL (pg/ml)	-1.852 (5.810)

Adverse events

Time frame: AEs were collected starting at screening through Day 364 Visit for each participant.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Active BCG Immunization	0 of 15 (0%)	1 of 15 (6.7%)	0 of 15

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 13 Apr 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

Related trials for Mild Cognitive Impairment

RecruitingPhase 1
PET Imaging of Phosphodiesterase-4 (PDE4) in Volunteers With Alzheimer Disease (AD) or Mild Cognitive Impairment (MCI)
Alzheimer s Disease, Mild Cognitive Impairment
RecruitingObservational study
Community-based Screening for Alzheimer's Disease
Alzheimer's Disease(AD), Mild Cognitive Impairment (MCI)
RecruitingObservational study
InRAD Observational Study
Alzheimer's Disease(AD), Mild Cognitive Impairment (MCI)
Recruiting
Treating Insomnia in Mild Cognitive Impairment
Mild Cognitive Impairment (MCI), Insomnia
Recruiting
Telehealth-Adapted Compensatory Training and Intervention for Cognition
MCI, Mild Cognitive Impairment

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 Arnold, MD 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 Biological/Vaccine: Bacillus Calmette-Guerin (BCG) in people with Mild Cognitive Impairment and Mild Dementia, run by Steven E Arnold, MD 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 22 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 13 Apr 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 13 Apr 2025). 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?

Blood Biomarkers of Pharmacodynamic Response- Cytokines (time frame: Baseline to Day 364). The study lists 14 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 NCT05004688, 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 13 Apr 2025.