Evaluation of a Computerized Complex Instrumental Activities of Daily Living Marker (NMI) as a Pre-Clinical or Pro-Dromal Alzheimers Diagnosis (Prognosis) for Optimum Outcomes
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- Altoida
- 入组人数
- 548
- 主要终点
- Change in Diagnostic Area Under the Receiver Operating Characteristic Curve (ROC-AUC)
研究概览
简要总结
The proposed study is designed to evaluate the performance of the ALTOIDA™ System as a tool to assist physicians in diagnosing Alzheimer's Disease (AD) in real-world clinical settings. The design of this study is guided by two overriding factors: 1) to optimize the performance of the ALTOIDA™ Neuro Motor Index (NMI) prognosis classifiers, the subjects making up the training sets must be well characterized as to their clinical diagnosis, and 2) all ALTOIDA™ tests must be performed and reproduced in real-world clinical settings.
Although there is already a large body of peer-reviewed scientific literature demonstrating that certain digital biomarker patterns are associated with certain neurologic conditions, the utilization of such tools for the evaluation of neurologic disorders is still considered an emerging science and therefore in the investigational stage. Although this protocol will report on brain patterns of certain neurologic conditions such as cognitive impairment and Alzheimer's disease, based on patterns published in peer-reviewed journals, such findings are not considered stand alone or diagnostic per se and should always be considered by the primary physician in conjunction with the patient's clinical condition. These data should only be used as additional information to add to the primary physician's diagnostic impression.
详细描述
The goal of the study is to determine relationships among the clinical, cognitive, imaging, genetic, and biochemical biomarker characteristics of the stage of the AD spectrum that precedes MCI, the mildest symptomatic phase of AD, referred to here as MCI. The ADNI-GO model posits that AD begins with amyloid β (Aβ) deposition in the cortex, which leads to synaptic dysfunction, neurodegeneration, and cognitive/ functional decline.
It may be possible to determine the future development of ALZ in a preclinical state in a cognitively normal but high risk individual at least 18-24 months before any symptoms develop of cognitive impairment. In addition a newly proposed research framework proposes to use biomarkers for amyloid, tau, and neurodegeneration (ATN) to classify MCI patients.
Some of the leading-edge technologies under study are brain-imaging techniques, such as positron emission tomography (PET), including FDG-PET (which measures glucose metabolism in the brain); PET using a radioactive compound (F-AV-45) that measures brain beta-amyloid; and structural MRI. Brain scans are showing scientists how the brain's structure and function change as AD starts and progresses. Biomarkers in cerebrospinal fluid are revealing other changes that could identify which patients with MCI will develop Alzheimer's. Scientists are looking at levels of beta-amyloid and tau in cerebrospinal fluid. (Abnormal amounts of the amyloid and tau proteins in the brain are hallmarks of Alzheimer's disease.)
The aim of the study is to evaluate the performance of the ALTOIDA™ System as as a tool to assist physicians in diagnosing Alzheimer's Disease (AD) in real-world clinical settings.
The study will be :
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 55 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Between 55 and 90 years of age
- •Study partner to accompany patient to all clinic visits for the duration of the protocol
- •Memory complaint by patient and/or study partner
- •Abnormal memory function score on Wechsler Memory Scale (adjusted for education)
- •Mini-Mental State Exam score between 24 and 30 (inclusive)
- •Clinical Dementia Rating = 0.5; Memory Box score at least 0.5
- •General cognition and functional performance sufficiently preserved such that a diagnosis of Alzheimer's disease cannot be made by the site physician at the time of the screening visit
- •Stability of the following permitted medications for 4 weeks (unless stated otherwise):
- •Antidepressants lacking significant anticholinergic side effects
- •Estrogen replacement therapy
- •Gingko biloba is permissible, but discouraged
- •Washout from psychoactive medication (e.g., excluded antidepressants, neuroleptics, chronic anxiolytics or sedative hypnotics, etc.) for at least 4 weeks prior to screening
- •Cholinesterase inhibitors and memantine if stable for 12 weeks prior to screening
- •Geriatric Depression Scale less than 6
- •Visual and auditory acuity adequate for neuropsychological testing
- •Good general health with no diseases expected to interfere with the study
- •Not pregnant, lactating, or of childbearing potential (i.e. women must be two years post-menopausal or surgically sterile)
- •Hachinski less than or equal to 4
- •Six grade education or has a good work history (sufficient to exclude mental retardation)
- •Fluent in English or Spanish
- •Agrees to at least one lumbar puncture for the collection of CSF
- •Willing and able to complete all baseline assessments
- •Willing to undergo repeated MRIs and at least two PET scans and willing to provide DNA and plasma samples as specified
- •Willing and able to participate in a longitudinal imaging study
排除标准
- •Any significant neurologic disease other than suspected incipient Alzheimer's disease, such as Parkinson's disease, multi-infarct dementia, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma followed by persistent neurologic defaults or known structural brain abnormalities
- •Screening/baseline MRI scans with evidence of infection, infarction, or other focal lesions; multiple lacunes or lacunes in a critical memory structure
- •Presence of pacemakers, aneurysm clips, artificial heart valves, ear implants, metal fragments or foreign objects in the eyes, skin or body
- •Major depression, bipolar disorder as described in DSM-IV within the past 1 year
- •Psychotic features, agitation or behavioral problems within the last 3 months which could lead to difficulty complying with the protocol
- •History of schizophrenia
- •History of alcohol or substance abuse or dependence within the past 2 years
- •Any significant systemic illness or unstable medical condition which could lead to difficulty complying with the protocol
- •Clinically significant abnormalities in B12, or TFTs that might interfere with the study
- •Residence in skilled nursing facility
- •Current use of specific psychoactive medications (e.g.,certain antidepressants, neuroleptics, chronic anxiolytics or sedative hypnotics, etc.); current use of warfarin (exclusionary for lumbar puncture)
- •Use of investigational agents one month prior to entry and for the duration of the trial
- •Exclusion for amyloid imaging with 18F -AV-45: Current or recent participation in any procedures involving radioactive agents such that the total radiation dose exposure to the participant in any given year would exceed the limits of annual and total dose commitment set forth in the US Code of Federal Regulations (CFR) Title 21 Section 361.1
- •Exceptions to these guidelines may be considered on a case-by-case basis at the discretion of the protocol director
结局指标
主要结局
Change in Diagnostic Area Under the Receiver Operating Characteristic Curve (ROC-AUC)
时间窗: approximately 40 months follow up
The machine learning models capturing voice data, hands micromovements \& micro-errors, posture changes, eye tracking, visuospatial navigation micro-errors and spatio-temporal gait parameters developed for the Altoida system will be tested in this prospective cohort. Sensitivity, specificity and accuracy of the model will be tested in differential diagnosis between the study groups as well as the accuracy of prediction cognitive decline as measured by neuropsychological test battery in the MCI group.
次要结局
- Change From Baseline in Clinical Measure 5(baseline, 6, 12, 24, 36 and approximately 40 months follow up)
- Change From Baseline in Clinical Measure 2(baseline, 6, 12, 24, 36 and approximately 40 months follow up)
- Secondary Resting State EEG Endpoints(baseline, 6, 12, 24, 36 and approximately 40 months follow up)
- Change From Baseline in Clinical Measure 3(baseline, 6, 12, 24, 36 and approximately 40 months follow up)
- Change From Baseline in Clinical Measure 4(baseline, 6, 12, 24, 36 and approximately 40 months follow up)
- Change From Baseline in Clinical Measure 6(baseline, 6, 12, 24, 36 and approximately 40 months follow up)
- Change From Baseline in Clinical Measure 7(baseline, 6, 12, 24, 36 and approximately 40 months follow up)
- Changes in Driving Direction(baseline, 6, 12, 24, 36 and approximately 40 months follow up)
- Change From Baseline in Clinical Measure 1(baseline, 6, 12, 24, 36 and 42 months of follow up)
- Secondary Resting State Auditory Oddball ERP Endpoints(baseline, 6, 12, 24, 36 and approximately 40 months follow up)
- Total Abeta 1-42 (Aβ42) Amyloid Deposition(baseline, 6, 12, 24, 36 and approximately 40 months follow up)
- Change of Brain Amyloid Deposition(baseline, 6, 12, 24, 36 and approximately 40 months follow up)
- MRI (Optional)(baseline, 6, 12, 24, 36 and approximately 40 months follow up)
- Changes in Driving Breaking Force(baseline, 6, 12, 24, 36 and approximately 40 months follow up)
- Changes in Driving Violations(Continuous measurement for approximately 12 months follow up)
- Change of CSF Biomarkers Tau and ptau181 Values(baseline, 6, 12, 24, 36 and approximately 40 months follow up)
- Changes in Driving Acceleration Velocity(baseline, 6, 12, 24, 36 and approximately 40 months follow up)
- Change From Baseline in Cognitive Measure(baseline, 6, 12, 24, 36 and approximately 40 months follow up)