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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.
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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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| BCG | Experimental | Active BCG immunization |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Biological/Vaccine: Bacillus Calmette-Guerin (BCG) | Biological | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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. | 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. | 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. | Baseline to Day 364 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Steven Arnold, MD | Massachusetts General Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Alzheimer's Clinical and Translational Research Unit | Charlestown | Massachusetts | 02129 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 42393277 | Derived | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Active BCG Immunization | Active BCG immunization 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Active BCG Immunization | Active BCG immunization 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Mean | Standard Deviation | picogram/milliliter (pg/ml) | Baseline to Day 364 |
|
AEs were collected starting at screening through Day 364 Visit for each participant.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Active BCG Immunization | Active BCG immunization 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. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Elevated Blood Pressure | Vascular disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Kayla McEachern | Mass General | 617 643 5265 | kmceachern2@mgh.harvard.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Oct 13, 2022 | Sep 11, 2023 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D060825 | Cognitive Dysfunction |
| D000544 | Alzheimer Disease |
| ID | Term |
|---|---|
| D003072 | Cognition Disorders |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D003704 | Dementia |
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| ID | Term |
|---|---|
| D001688 | Biological Products |
| D001500 | BCG Vaccine |
| ID | Term |
|---|---|
| D045424 | Complex Mixtures |
| D032581 | Tuberculosis Vaccines |
| D001428 | Bacterial Vaccines |
| D014612 | Vaccines |
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open-label
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|
| 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | Baseline to Day 84 |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| CSF Collected | Count of Participants | Participants |
|
| Blood Collected | Count of Participants | Participants |
|
| Cognitive testing measured | Count of Participants | Participants |
|
| Units | Counts |
|---|---|
| Participants |
|
|
| Primary | 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. | 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. | Posted | Mean | Standard Deviation | picogram/milliliter (pg/ml) | Baseline to Day 84 |
|
|
|
| Primary | 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. | Posted | Mean | Standard Deviation | picogram/milliliter (pg/ml) | Baseline to Day 364 |
|
|
|
| Primary | 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. | Posted | Mean | Standard Deviation | picogram/milliliter (pg/ml) | Baseline to Day 364 |
|
|
|
| Primary | 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. | Posted | Mean | Standard Deviation | picogram/milliliter (pg/ml) | Baseline to Day 364 |
|
|
|
| Primary | 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. | 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. | Posted | Mean | Standard Deviation | picogram/milliliter (pg/ml) | Baseline to Day 84 |
|
|
|
| Primary | 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. | 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. | Posted | Mean | Standard Deviation | picogram/milliliter (pg/ml) | Baseline to Day 84 |
|
|
|
| Primary | 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. | 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. | Posted | Mean | Standard Deviation | score on a scale | Baseline to Day 84 |
|
|
|
| Primary | 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. | Posted | Mean | Standard Deviation | score on a scale | Baseline to Day 364 |
|
|
|
| Primary | Amyloid-β42/40 Average Difference in Blood | Average difference of ATN markers of AD pathophysiology (Amyloid-β42/40 ratio) in blood from baseline. | Posted | Mean | Standard Deviation | ratio | Baseline to Day 364 |
|
|
|
| Primary | Amyloid-β42/40 Average Difference in CSF | Average difference of ATN markers of AD pathophysiology (Amyloid-β42/40) in CSF from baseline. | Posted | Mean | Standard Deviation | ratio | Baseline to Day 364 |
|
|
|
| Primary | 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. | 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. | Posted | Mean | Standard Deviation | ratio | Baseline to Day 84 |
|
|
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| Primary | 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. | 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. | Posted | Mean | Standard Deviation | ratio | Baseline to Day 84 |
|
|
|
| Primary | 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. | 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. | Posted | Mean | Standard Deviation | picograms/mililiter (pg/ml) | Baseline to Day 84 |
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| 0 |
| 15 |
| 0 |
| 15 |
| 1 |
| 15 |
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| D001927 |
| Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D024801 | Tauopathies |
| D019636 | Neurodegenerative Diseases |
| Title | Measurements |
|---|---|
|
| CSF IL-6 (pg/ml) |
|
| CSF IL-10 (pg/ml) |
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| CSF TNF-a (pg/ml) |
|
| Title | Measurements |
|---|---|
|
| CSF IL-6 (pg/ml) |
|
| CSF IL-10 (pg/ml) |
|
| CSF TNF-a (pg/ml) |
|
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|
| Plasma IL-6 (pg/ml) |
|
| Plasma IL-10 (pg/ml) |
|
| Plasma TNF-a (pg/ml) |
|