<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04507126</url>
  </required_header>
  <id_info>
    <org_study_id>2020P002042</org_study_id>
    <nct_id>NCT04507126</nct_id>
  </id_info>
  <brief_title>A Pilot Study of the Effects of Bacillus Calmette-Guérin (BCG) Immunization on Cerebrospinal Fluid and Blood-based Biomarkers in Older Adults.</brief_title>
  <official_title>Effects of BCG Immunization on Cerebrospinal Fluid and Blood-Based Biomarkers in Older Adults: A Pilot</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Massachusetts General Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Massachusetts General Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      A pilot study of the effects of Bacillus Calmette-Guérin (BCG) immunization on cerebrospinal&#xD;
      fluid and blood-based biomarkers in older adults.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This single-site, open-label clinical trial will investigate the immune and neurobiological&#xD;
      effects of BCG vaccination in cognitively unimpaired older adults and older adults with&#xD;
      memory and thinking problems by measuring target engagement, pharmacodynamic response, and&#xD;
      effect on Alzheimer's disease (AD) pathology and immune response markers. This study will&#xD;
      also gather data on study feasibility, tolerability, and safety.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 1, 2021</start_date>
  <completion_date type="Actual">April 1, 2022</completion_date>
  <primary_completion_date type="Actual">April 1, 2022</primary_completion_date>
  <phase>Early Phase 1</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>CSF biomarkers of pharmacodynamic response- cytokines</measure>
    <time_frame>Day 84</time_frame>
    <description>Change in concentration of circulating cytokines in CSF from baseline</description>
  </primary_outcome>
  <primary_outcome>
    <measure>CSF biomarkers of AD pathology-ATN</measure>
    <time_frame>Day 84</time_frame>
    <description>Change in concentration of ATN markers of AD pathophysiology (Amyloid-β42/40, phospho-tau, total tau and neurofilament light protein biomarkers) in CSF from baseline.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Blood biomarkers of pharmacodynamic response- cytokines</measure>
    <time_frame>Day 28</time_frame>
    <description>Change in concentration of circulating cytokines in blood from baseline.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Blood biomarkers of pharmacodynamic response- cytokines</measure>
    <time_frame>Day 84</time_frame>
    <description>Change in concentration of circulating cytokines in blood from baseline</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Blood biomarkers of AD pathology</measure>
    <time_frame>Day 28</time_frame>
    <description>Change in concentration of ATN markers of AD pathophysiology (Amyloid-β42/40, phospho-tau, total tau and neurofilament light protein biomarkers) in blood from baseline.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Blood biomarkers of AD pathology</measure>
    <time_frame>Day 84</time_frame>
    <description>Change in concentration of ATN markers of AD pathophysiology (Amyloid-β42/40, phospho-tau, total tau and neurofilament light protein biomarkers) in blood from baseline.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cognitive Measures (RBANS)</measure>
    <time_frame>Day 84</time_frame>
    <description>Change from baseline in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) score</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Mild Cognitive Impairment</condition>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>BCG Immunization</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Bacillus Calmette-Guerin (BCG)</intervention_name>
    <description>Vaccine</description>
    <arm_group_label>BCG Immunization</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Study subjects meeting all the following criteria will be allowed to enroll in the study:&#xD;
&#xD;
          1. Age 55-80 inclusive;&#xD;
&#xD;
          2. MoCA ≥18;&#xD;
&#xD;
          3. Normal cognition as defined by MoCA ≥ 26 or MCI as defined by the NIA-AA Workgroup&#xD;
             (2011) and MoCA score between 18 and 25 (inclusive);&#xD;
&#xD;
          4. Education level, English language skills, and literacy indicates subject will be able&#xD;
             to complete all assessments;&#xD;
&#xD;
          5. Ability to provide informed consent;&#xD;
&#xD;
          6. Willing and able to complete all assessment and study procedures, including blood&#xD;
             draws, lumbar punctures, and clinical assessments;&#xD;
&#xD;
          7. If on cholinesterase inhibitor and/or memantine, doses are stable for 3 months prior&#xD;
             to baseline;&#xD;
&#xD;
          8. Negative test results for HIV antibody and Tuberculosis (QuantiFERON) at screening;&#xD;
&#xD;
          9. No prior BCG exposure either through birth vaccinations (born in North American) or&#xD;
             BCG bladder cancer treatment.&#xD;
&#xD;
         10. Documentation of current flu season vaccination dated at least 60 days prior to&#xD;
             baseline visit.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Study subjects meeting any of the following criteria will not be allowed to enroll in the&#xD;
        study:&#xD;
&#xD;
          1. History of chronic infectious disease, such as HIV or untreated or active hepatitis;&#xD;
&#xD;
          2. History of tuberculosis, positive interferon-gamma release assay (IGRA, also known as&#xD;
             the QuantiFERON-TB test), including a test with a high reactivity to mycobacteria of&#xD;
             non-tuberculosis variety;&#xD;
&#xD;
          3. Prior BCG vaccination, positive T-spot tuberculosis test or a T-spot test showing&#xD;
             significant Mycobacteria exposure;&#xD;
&#xD;
          4. A positive SARS-CoV-2 PCR result within 3 months of screening, or known close contact&#xD;
             with a confirmed COVID-19 positive person or symptoms highly suspicious for COVID-19&#xD;
             (per CDC guidelines) within 1 month of screening, including fever, cough, shortness of&#xD;
             breath, chills, muscle pain, new loss of taste or smell, vomiting or diarrhea, and/or&#xD;
             sore throat, based on clinician's judgment;&#xD;
&#xD;
          5. History of treatment with metformin within the past one year;&#xD;
&#xD;
          6. Previous participation (ever) in active immunization research for AD or passive&#xD;
             immunotherapy or other disease-modifying treatments for AD within the past three&#xD;
             months;&#xD;
&#xD;
          7. Current treatment with immunosuppressants (calcineurin inhibitors, corticosteroids, or&#xD;
             biological or cytotoxic immunosuppressants, or disease or condition likely to require&#xD;
             high dose steroid or immunosuppressive therapy);&#xD;
&#xD;
          8. Other conditions or treatments associated with increased risk of infections or&#xD;
             treatment with immunosuppressive medications for any reason;&#xD;
&#xD;
          9. Current treatment with aspirin &gt; 160 mg/day or chronic, daily NSAIDs;&#xD;
&#xD;
         10. Chronic use of antibiotics;&#xD;
&#xD;
         11. History of keloid formation;&#xD;
&#xD;
         12. Living with someone who is immunosuppressed and/or at high risk for infectious&#xD;
             diseases (for example, HIV+ or taking immunosuppressive medications for any reason),&#xD;
             or in a job (e.g. healthcare) in which the subject works with immunosuppressed&#xD;
             populations;&#xD;
&#xD;
         13. Other/confounding neurological or psychiatric condition, unstable medical or&#xD;
             psychiatric conditions, contraindications to BCG use and lab abnormalities or&#xD;
             concurrent medication use posing risk for BCG or study procedures;&#xD;
&#xD;
         14. Laboratory abnormalities in B12, Folate, TSH, or other common laboratory parameters&#xD;
             that may contribute to cognitive dysfunction;&#xD;
&#xD;
         15. Laboratory abnormalities in CBC, electrolytes, LFTs, BUN, Cr, total serum&#xD;
             immunoglobulins, ESR, CRP, or urinalysis posing risk to treatment with BCG per&#xD;
             clinician judgment;&#xD;
&#xD;
         16. Laboratory abnormalities in PT-INR, which would pose a risk to performing the lumbar&#xD;
             puncture procedure;&#xD;
&#xD;
         17. Discontinuation of cholinesterase inhibitor or memantine within one month (28 days)&#xD;
             prior to baseline visit;&#xD;
&#xD;
         18. Females who are pregnant, lactating or of child-bearing potential;&#xD;
&#xD;
         19. If male with female partner(s) of childbearing potential, unwilling or unable to&#xD;
             adhere to contraception requirements specified in the protocol.&#xD;
&#xD;
         20. Administration of live vaccine &lt;60 days prior to Baseline.&#xD;
&#xD;
         21. Increased intracranial pressure as determined on a fundoscopy/neurological examination&#xD;
             performed within 30 days of LP;&#xD;
&#xD;
         22. COVID-19 vaccination &lt; 60 days prior to baseline or within 14 days of BCG&#xD;
             immunizations.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>55 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Steven E Arnold, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Massachusetts General Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Denise Faustman, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Massachusetts General Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Clinical Translational Research Unit</name>
      <address>
        <city>Charlestown</city>
        <state>Massachusetts</state>
        <zip>02124</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>June 23, 2020</study_first_submitted>
  <study_first_submitted_qc>August 6, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 11, 2020</study_first_posted>
  <last_update_submitted>January 26, 2023</last_update_submitted>
  <last_update_submitted_qc>January 26, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 27, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Massachusetts General Hospital</investigator_affiliation>
    <investigator_full_name>Steven E Arnold, MD</investigator_full_name>
    <investigator_title>Professor of Neurology</investigator_title>
  </responsible_party>
  <keyword>Cognition</keyword>
  <keyword>Alzheimer's disease</keyword>
  <keyword>Memory</keyword>
  <keyword>BCG</keyword>
  <keyword>Immunization</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cognitive Dysfunction</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>BCG Vaccine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>April 2, 2023</submitted>
    <returned>April 24, 2023</returned>
    <submitted>May 19, 2023</submitted>
    <returned>June 13, 2023</returned>
    <submitted>July 10, 2023</submitted>
    <returned>July 27, 2023</returned>
    <submitted>August 10, 2023</submitted>
    <returned>August 29, 2023</returned>
    <submitted>September 8, 2023</submitted>
  </pending_results>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04507126
org study id: 2020P002042
nct id: NCT04507126
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
A pilot study of the effects of Bacillus Calmette-Guérin (BCG) immunization on cerebrospinal
      fluid and blood-based biomarkers in older adults.
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.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Other
masking: None (Open Label)
measure: CSF biomarkers of pharmacodynamic response- cytokines
time frame: Day 84
description: Change in concentration of circulating cytokines in CSF from baseline
measure: CSF biomarkers of AD pathology-ATN
time frame: Day 84
description: Change in concentration of ATN markers of AD pathophysiology (Amyloid-β42/40, phospho-tau, total tau and neurofilament light protein biomarkers) in CSF from baseline.
measure: Blood biomarkers of pharmacodynamic response- cytokines
time frame: Day 28
description: Change in concentration of circulating cytokines in blood from baseline.
measure: Blood biomarkers of pharmacodynamic response- cytokines
time frame: Day 84
description: Change in concentration of circulating cytokines in blood from baseline
measure: Blood biomarkers of AD pathology
time frame: Day 28
description: Change in concentration of ATN markers of AD pathophysiology (Amyloid-β42/40, phospho-tau, total tau and neurofilament light protein biomarkers) in blood from baseline.
measure: Blood biomarkers of AD pathology
time frame: Day 84
description: Change in concentration of ATN markers of AD pathophysiology (Amyloid-β42/40, phospho-tau, total tau and neurofilament light protein biomarkers) in blood from baseline.
measure: Cognitive Measures (RBANS)
time frame: Day 84
description: Change from baseline in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) score
arm group label: BCG Immunization
arm group type: Experimental
description: 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.
intervention type: Biological
intervention name: Bacillus Calmette-Guerin (BCG)
description: Vaccine
arm group label: BCG Immunization
criteria: 
gender: All
minimum age: 55 Years
maximum age: 80 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Steven E Arnold, MD
role: Principal Investigator
affiliation: Massachusetts General Hospital
last name: Denise Faustman, MD, PhD
role: Principal Investigator
affiliation: Massachusetts General Hospital
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Massachusetts General Hospital
investigator full name: Steven E Arnold, MD
investigator title: Professor of Neurology
mesh term: Cognitive Dysfunction
mesh term: BCG Vaccine
sharing ipd: No
submitted: April 2, 2023
returned: April 24, 2023
submitted: May 19, 2023
returned: June 13, 2023
submitted: July 10, 2023
returned: July 27, 2023
submitted: August 10, 2023
returned: August 29, 2023
submitted: September 8, 2023