NCT04263519撤回2 期
A Pilot Open Labeled Study of Tacrolimus to Assess it's Effects on Bio-markers of Mild Cognitive Impairment and Alzheimer's Disease
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 主要终点
- CSF biomarkers of target engagement, AD pathology, and neurodegeneration
研究概览
简要总结
A Pilot open labeled study of Tacrolimus in Alzheimer's Disease.
详细描述
This study will investigate the neurobiological effect of tacrolimus in persons with MCI and dementia due to AD by measuring biomarkers of target engagement in immune response, amyloid-b, tau and neurodegeneration in CSF, functional connectivity with MRI and EEG, and cognition. Study objectives include:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 55 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Study subjects meeting all of the following criteria will be allowed to enroll in the study:
- •Age 55-85 inclusive, male or female.
- •Diagnosis of MCI or dementia due to AD as shown by positive AD biomarker (CSF or neuroimaging).
- •Education level, English language skills and literacy indicates subject will be able to complete all assessments.
- •Willing and able to complete all assessment and study procedures, including phlebotomies, lumbar punctures, MRIs, neurocognitive testing.
- •Subject has a study partner with at least two days of contact per week and willingness to assist with subject's research activities.
- •If on cholinesterase inhibitor and/or memantine, doses are stable for 3 months prior to baseline.
排除标准
- •Subjects meeting any of the following criteria during the screening evaluation will be excluded:
- •Allergy or hypersensitivity to tacrolimus.
- •Any specific CNS disease other than suspected AD, such as major clinical stroke, brain tumor, normal pressure hydrocephalus, multiple sclerosis, significant head trauma with persistent neurological of cognitive deficits or complaints, Parkinson's disease, frontotemporal dementia, and/or other neurodegenerative diseases.
- •Any significant systemic illness or clinically significant unstable medical condition that could affect subject safety or compliance with the study; including but not limited to any active infection, active malignancy except non-melanomatous skin cancers, cirrhosis, active hepatitis, uncontrolled diabetes (A1c >8), AIDS, common variable immunodeficiency, conditions treated with biologics, uncontrolled hypertension, chronic kidney disease with an eGFR <45 ml/min, Platelets < 100K, Hgb <
- •History of alcohol or other substance abuse or dependence with the past two years.
- •Major active psychiatric illness (e.g. depression, bipolar disorder, obsessive compulsive disorder, schizophrenia) within the previous year.
- •Current suicidal ideation or history of suicide attempt.
- •Contraindications to undergo MRI studies:
- •History of a cardiac pacemaker or pacemaker wires,
- •Metallic particles in the body,
- •Vascular clips in the head,
- •Prosthetic heart valves, or
- •Severe claustrophobia impeding ability to participate in an imaging study.
- •MRI findings that show one or more of the following:
- •More than 4 incidental microhemorrhages,
- •Incidental lacunar infarcts with attributable signs or symptoms and with history of stroke,
- •Incidental meningiomas with attributable signs or symptoms, or
- •Newly recognized meningioma.
- •Laboratory abnormalities in B12, TSH, or other common laboratory parameters that may contribute to cognitive dysfunction.
- •Laboratory abnormalities in PT-INR, CBC, electrolytes, magnesium, LFTs, BUN, Cr or others, or abnormalities in ECG posing risk to treatment with tacrolimus.
- •Current use of medications with psychoactive properties (e.g., anticholinergics, antihistamines, antipsychotics, sedative hypnotics, anxiolytics) that may deleteriously affect cognition in the judgement of the investigator.
- •Current use of medications that interact with tacrolimus (protease inhibitors, macrolides, rifampin, barbiturates, phenytoin, or azoles).
- •Inability to avoid any dietary supplements that could interact with tacrolimus metabolism.
- •Inability to avoid grapefruit and grapefruit juice.
- •Use of other small molecule or device-based investigational agents one month prior to entry and for the duration of the trial; or participation in any immunotherapy clinical trial within three months prior to baseline visit.
- •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
研究组 & 干预措施
Low Serum Level
Active Comparator
Stable Blood Tacrolimus of 2-5 ng/ml.
干预措施: Tacrolimus (Drug)
High Serum Level
Active Comparator
Stable Blood Tacrolimus of 5.1-10 ng/ml.
干预措施: Tacrolimus (Drug)
结局指标
主要结局
CSF biomarkers of target engagement, AD pathology, and neurodegeneration
时间窗: Baseline and 12 weeks
Evaluate effect of tacrolimus on molecular markers of target engagement (calcineurin/NFAT mediated inflammatory markers IL-2, IL-6, IFNβ and YKL-40), AD pathology (amyloid-β, tau, phospho-tau) and neurodegeneration (neurofilament-light, neurogranin). We will measure change from baseline in all CSF biomarkers following 12 weeks of steady treatment.
次要结局
- Blood biomarkers of target engagement, AD pathology, and neurodegeneration.(Baseline and 12 weeks)
- Structural neuroimaging of Hippocampal volume.(Baseline and 12 weeks)
- Functional neuroimaging of default mode network connectivity.(Baseline and 12 weeks)
- Electroencephalograms (EEG) spectral power(Baseline and 12 weeks)
- Montreal Cognitive Assessment (MoCA)(Baseline and 12 weeks)
- Neuropsychiatric Inventory Questionnaire (NPIQ)(Baseline, 4 weeks, 8 weeks and 12 weeks)
- Functional Activities Questionnaire (FAQ)(Baseline, 4 weeks, 8 weeks and 12 weeks)
- Repeated Battery for the Assessment of Neuropsychological Status(Baseline, 4 weeks, 8 weeks and 12 weeks)
研究者
Steven E Arnold
Manager Director Phsycian
Massachusetts General Hospital
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