Alzheimer Disease, Mild Cognitive Impairment, Mild Dementia, Moderate Dementia
Conditions
Brief 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.
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.
Interventions
BIOLOGICALBiological/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.
Sponsors
Steven E Arnold, MD
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Intervention model description
open-label
Eligibility
Sex/Gender
ALL
Age
55 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1. Individuals between the ages of 55-85; 2. MCI or moderate dementia due to AD as defined by the 2011 NIA-AA Workgroup recommendations; 3. MoCA ≥ 8 at screening; 4. Global CDR between 0.5-2 (inclusive) at screening; 5. Amyloid and/or tau biomarkers indicative of AD pathology; 6. Education level, English language skills and literacy indicates subject will be able to complete all assessments; 7. 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; 8. Willing and able to complete all assessment and study procedures, including blood and lumbar punctures, and clinical assessments; 9. If on cholinesterase inhibitor and/or memantine, doses are stable for 3 months prior to baseline; 10. Negative test results for HIV antibody and Tuberculosis (QuantiFERON) at screening; 11. No prior BCG exposure either through birth vaccinations (born in North American) or BCG bladder cancer treatment.
Exclusion criteria
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. Treatment with other investigational agents which, at the discretion of the investigator, interfere with safety and/or study outcomes; 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. Current (as of time of study screening) or 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 per clinician judgment; 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 within 30 days of screening visit or BCG immunizations 21. Administration of non-live vaccine within 14 days of screening visit or BCG immunizations 22. If participating in optional MRI: Existing contraindication to MRI per MGH Athinoula A. Martinos Center research guidelines
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Amyloid-β42/40 Average Difference in Blood - Baseline to Day 84 | 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 | 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 | 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 | 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. |
| Blood Biomarkers of AD Pathology-ATN | 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 | 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. |
| Cognitive Measures (RBANS) | 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. |
| Amyloid-β42/40 Average Difference in Blood | 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 | Baseline to Day 364 | Average difference of ATN markers of AD pathophysiology (Amyloid-β42/40) in CSF from baseline. |
| Blood Biomarkers of Pharmacodynamic Response - Cytokines | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 15 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Physician Decision | 2 |
| Overall Study | Protocol Violation | 7 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Active BCG Immunization |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 10 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants |
| Blood Collected | 7 Participants |
| Cognitive testing measured | 7 Participants |
| CSF Collected | 7 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 15 Participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 15 |
| other Total, other adverse events | 1 / 15 |
| serious Total, serious adverse events | 0 / 15 |
Outcome results
Primary
Amyloid-β42/40 Average Difference in Blood
Average difference of ATN markers of AD pathophysiology (Amyloid-β42/40 ratio) in blood from baseline.
Time frame: Baseline to Day 364
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active BCG Immunization | Amyloid-β42/40 Average Difference in Blood | -0.001 ratio | Standard Deviation 0.06 |
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.
Time frame: Baseline to Day 84
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active BCG Immunization | Amyloid-β42/40 Average Difference in Blood - Baseline to Day 84 | 0.001 ratio | Standard Deviation 0.005 |
Primary
Amyloid-β42/40 Average Difference in CSF
Average difference of ATN markers of AD pathophysiology (Amyloid-β42/40) in CSF from baseline.
Time frame: Baseline to Day 364
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active BCG Immunization | Amyloid-β42/40 Average Difference in CSF | 0.000 ratio | Standard Deviation 0.002 |
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.
Time frame: Baseline to Day 84
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active BCG Immunization | Amyloid-β42/40 Average Difference in CSF - Baseline to Day 84 | -0.001 ratio | Standard Deviation 0.001 |
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.
Time frame: Baseline to Day 364
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active BCG Immunization | Blood Biomarkers of AD Pathology-ATN | Plasma pTau217 (pg/ml) | -1.392 picogram/milliliter (pg/ml) | Standard Deviation 5.382 |
| Active BCG Immunization | Blood Biomarkers of AD Pathology-ATN | Plasma pTau181 (pg/ml) | 0.233 picogram/milliliter (pg/ml) | Standard Deviation 0.362 |
| Active BCG Immunization | Blood Biomarkers of AD Pathology-ATN | Plasma NfL (pg/ml) | -1.852 picogram/milliliter (pg/ml) | Standard Deviation 5.81 |
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.
Time frame: Baseline to Day 84
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active BCG Immunization | Blood Biomarkers of AD Pathology-ATN | Plasma pTau217 (pg/ml) | 0.916 picogram/milliliter (pg/ml) | Standard Deviation 7.179 |
| Active BCG Immunization | Blood Biomarkers of AD Pathology-ATN | Plasma pTau181 (pg/ml) | 0.004 picogram/milliliter (pg/ml) | Standard Deviation 1.288 |
| Active BCG Immunization | Blood Biomarkers of AD Pathology-ATN | Plasma NfL (pg/ml) | -1.735 picogram/milliliter (pg/ml) | Standard Deviation 7.881 |
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.
Time frame: Baseline to Day 84
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active BCG Immunization | Blood Biomarkers of Pharmacodynamic Response - Cytokines | Plasma IFN-g (pg/ml) | 365.612 picograms/mililiter (pg/ml) | Standard Deviation 926.852 |
| Active BCG Immunization | Blood Biomarkers of Pharmacodynamic Response - Cytokines | Plasma IL-1b (pg/ml) | -24.320 picograms/mililiter (pg/ml) | Standard Deviation 100.242 |
| Active BCG Immunization | Blood Biomarkers of Pharmacodynamic Response - Cytokines | Plasma IL-2 (pg/ml) | 0.460 picograms/mililiter (pg/ml) | Standard Deviation 48.615 |
| Active BCG Immunization | Blood Biomarkers of Pharmacodynamic Response - Cytokines | Plasma IL-6 (pg/ml) | -530.279 picograms/mililiter (pg/ml) | Standard Deviation 1926.387 |
| Active BCG Immunization | Blood Biomarkers of Pharmacodynamic Response - Cytokines | Plasma IL-10 (pg/ml) | 97.486 picograms/mililiter (pg/ml) | Standard Deviation 269.749 |
| Active BCG Immunization | Blood Biomarkers of Pharmacodynamic Response - Cytokines | Plasma TNF-a (pg/ml) | 12.004 picograms/mililiter (pg/ml) | Standard Deviation 151.302 |
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.
Time frame: Baseline to Day 364
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active BCG Immunization | Blood Biomarkers of Pharmacodynamic Response- Cytokines | Plasma IFN-g (pg/ml) | 26.672 picogram/milliliter (pg/ml) | Standard Deviation 125.864 |
| Active BCG Immunization | Blood Biomarkers of Pharmacodynamic Response- Cytokines | Plasma IL-1b (pg/ml) | 190.829 picogram/milliliter (pg/ml) | Standard Deviation 181.329 |
| Active BCG Immunization | Blood Biomarkers of Pharmacodynamic Response- Cytokines | Plasma IL-2 (pg/ml) | 20.309 picogram/milliliter (pg/ml) | Standard Deviation 19.205 |
| Active BCG Immunization | Blood Biomarkers of Pharmacodynamic Response- Cytokines | Plasma IL-6 (pg/ml) | 2293.879 picogram/milliliter (pg/ml) | Standard Deviation 4308.539 |
| Active BCG Immunization | Blood Biomarkers of Pharmacodynamic Response- Cytokines | Plasma IL-10 (pg/ml) | 366.090 picogram/milliliter (pg/ml) | Standard Deviation 656.157 |
| Active BCG Immunization | Blood Biomarkers of Pharmacodynamic Response- Cytokines | Plasma TNF-a (pg/ml) | 53.903 picogram/milliliter (pg/ml) | Standard Deviation 54.002 |
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.
Time frame: Baseline to Day 364
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active BCG Immunization | Cognitive Measures (RBANS) | -5.667 score on a scale | Standard Deviation 19.075 |
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.
Time frame: Baseline to Day 84
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active BCG Immunization | Cognitive Measures (RBANS) | 17.710 score on a scale | Standard Deviation 35.127 |
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.
Time frame: Baseline to Day 84
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active BCG Immunization | CSF Biomarkers of AD Pathology-ATN | CSF tTau (pg/ml) | 8.727 picogram/milliliter (pg/ml) | Standard Deviation 49.826 |
| Active BCG Immunization | CSF Biomarkers of AD Pathology-ATN | CSF pTau181 (pg/ml) | -2.414 picogram/milliliter (pg/ml) | Standard Deviation 11.793 |
| Active BCG Immunization | CSF Biomarkers of AD Pathology-ATN | CSF NfL (pg/ml) | -103.161 picogram/milliliter (pg/ml) | Standard Deviation 317.523 |
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.
Time frame: Baseline to Day 364
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active BCG Immunization | CSF Biomarkers of AD Pathology-ATN | CSF tTau (pg/ml) | -3.595 picogram/milliliter (pg/ml) | Standard Deviation 26.97 |
| Active BCG Immunization | CSF Biomarkers of AD Pathology-ATN | CSF pTau181 (pg/ml) | -5.955 picogram/milliliter (pg/ml) | Standard Deviation 10.135 |
| Active BCG Immunization | CSF Biomarkers of AD Pathology-ATN | CSF NfL (pg/ml) | -55.413 picogram/milliliter (pg/ml) | Standard Deviation 477.315 |
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.
Time frame: Baseline to Day 364
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active BCG Immunization | CSF Biomarkers of Pharmacodynamic Response- Cytokines | CSF IFN-g (pg/ml) | -14.368 picogram/milliliter (pg/ml) | Standard Deviation 13.773 |
| Active BCG Immunization | CSF Biomarkers of Pharmacodynamic Response- Cytokines | CSF IL-1b (pg/ml) | 5.510 picogram/milliliter (pg/ml) | Standard Deviation 10.867 |
| Active BCG Immunization | CSF Biomarkers of Pharmacodynamic Response- Cytokines | CSF IL-2 (pg/ml) | -12.910 picogram/milliliter (pg/ml) | Standard Deviation 22.841 |
| Active BCG Immunization | CSF Biomarkers of Pharmacodynamic Response- Cytokines | CSF IL-6 (pg/ml) | 710.455 picogram/milliliter (pg/ml) | Standard Deviation 1827.73 |
| Active BCG Immunization | CSF Biomarkers of Pharmacodynamic Response- Cytokines | CSF IL-10 (pg/ml) | -95.078 picogram/milliliter (pg/ml) | Standard Deviation 144.162 |
| Active BCG Immunization | CSF Biomarkers of Pharmacodynamic Response- Cytokines | CSF TNF-a (pg/ml) | 0.300 picogram/milliliter (pg/ml) | Standard Deviation 19.083 |
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.
Time frame: Baseline to Day 84
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active BCG Immunization | CSF Biomarkers of Pharmacodynamic Response- Cytokines | CSF IFN-g (pg/ml) | 0.053 picogram/milliliter (pg/ml) | Standard Deviation 13.002 |
| Active BCG Immunization | CSF Biomarkers of Pharmacodynamic Response- Cytokines | CSF IL-1b (pg/ml) | -1.287 picogram/milliliter (pg/ml) | Standard Deviation 15.192 |
| Active BCG Immunization | CSF Biomarkers of Pharmacodynamic Response- Cytokines | CSF IL-2 (pg/ml) | 8.103 picogram/milliliter (pg/ml) | Standard Deviation 20.326 |
| Active BCG Immunization | CSF Biomarkers of Pharmacodynamic Response- Cytokines | CSF IL-6 (pg/ml) | 21.009 picogram/milliliter (pg/ml) | Standard Deviation 1220.991 |
| Active BCG Immunization | CSF Biomarkers of Pharmacodynamic Response- Cytokines | CSF IL-10 (pg/ml) | -3.057 picogram/milliliter (pg/ml) | Standard Deviation 80.133 |
| Active BCG Immunization | CSF Biomarkers of Pharmacodynamic Response- Cytokines | CSF TNF-a (pg/ml) | -0.396 picogram/milliliter (pg/ml) | Standard Deviation 11.426 |