A Trial to Evaluate the Effects of BCG in Adults With MCI and Mild-to-Moderate AD
2023年2月2日 更新者:Steven E Arnold, MD
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
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.
研究概览
详细说明
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.
研究类型
介入性
注册 (预期的)
15
阶段
- 阶段2
联系人和位置
本节提供了进行研究的人员的详细联系信息,以及有关进行该研究的地点的信息。
学习地点
-
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Massachusetts
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Charlestown、Massachusetts、美国、02129
- Alzheimer's Clinical and Translational Research Unit
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参与标准
研究人员寻找符合特定描述的人,称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
55年 至 85年 (成人、年长者)
接受健康志愿者
不
有资格学习的性别
全部
描述
Inclusion Criteria:
- 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;
- 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.
Exclusion Criteria:
- 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;
- 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
学习计划
本节提供研究计划的详细信息,包括研究的设计方式和研究的衡量标准。
研究是如何设计的?
设计细节
- 主要用途:其他
- 分配:不适用
- 介入模型:单组作业
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
---|---|
实验性的:BCG
Active BCG immunization
|
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.
其他名称:
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研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
---|---|---|
药效反应的脑脊液生物标志物-细胞因子
大体时间:第84天
|
CSF 中循环细胞因子浓度相对于基线的变化
|
第84天
|
药效学反应的血液生物标志物-细胞因子
大体时间:第84天
|
血液中循环细胞因子浓度相对于基线的变化
|
第84天
|
认知测量 (RBANS)
大体时间:第84天
|
用于评估神经心理状态 (RBANS) 评分的可重复电池相对于基线的变化
|
第84天
|
Blood biomarkers of pharmacodynamic response- cytokines
大体时间:Day 364
|
Change in concentration of circulating cytokines in blood from baseline
|
Day 364
|
CSF biomarkers of pharmacodynamic response- cytokines
大体时间:Day 364
|
Change in concentration of circulating cytokines in CSF from baseline
|
Day 364
|
Blood biomarkers of AD pathology-ATN
大体时间:Day 364
|
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
|
Day 364
|
CSF biomarkers of AD pathology-ATN
大体时间:Day 364
|
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
|
Day 364
|
Blood biomarkers of AD pathology-ATN
大体时间:Day 84
|
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
|
Day 84
|
CSF biomarkers of AD pathology-ATN
大体时间:Day 84
|
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
|
Day 84
|
Cognitive Measures (RBANS)
大体时间:Day 364
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Change from baseline in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) score
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Day 364
|
合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
调查人员
- 首席研究员:Steven Arnold, MD、Massachusetts General Hospital
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查,以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始 (实际的)
2022年3月25日
初级完成 (预期的)
2023年10月1日
研究完成 (预期的)
2023年10月1日
研究注册日期
首次提交
2021年8月6日
首先提交符合 QC 标准的
2021年8月6日
首次发布 (实际的)
2021年8月13日
研究记录更新
最后更新发布 (实际的)
2023年2月3日
上次提交的符合 QC 标准的更新
2023年2月2日
最后验证
2023年2月1日
更多信息
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