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Evaluation of a Computerized Complex Instrumental Activities of Daily Living Marker (NMI) (AltoidaML)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02843529
Recruitment Status : Completed
First Posted : July 26, 2016
Last Update Posted : May 27, 2020
Sponsor:
Collaborators:
Greek Alzheimer's Association and Related Disorders
University of Roma La Sapienza
IRCCS Centro San Giovanni di Dio Fatebenefratelli
Neuromed IRCCS
Scripps Health
Global Brain Health Institute (GBHI)
Takeda Pharmaceuticals International, Inc.
Research Center on Computational Biomarkers (RCCBM)
BiHELab - Bioinformatics and Human Electrophysiology Lab
Fundacion Clinic per a la Recerca Biomédica
University of Dublin, Trinity College
University of Barcelona
EIT Health
Klinik Hirslanden, Zurich
Center for BrainHealth - The University of Texas at Dallas
Information provided by (Responsible Party):
Altoida

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Alzheimer Disease Mild Cognitive Impairment Memory Disorders Cognitive Impairment Dementia Presymptomatic Disease Other: Altoida: neuropsychological, MRI, EEG and CSF biomarkers Not Applicable

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 548 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Adults at high risk of developing ALZ within 18-40 months (MCI) or cognitively normal for their age sex matching group. Risk factors include parents with a history of ALZ, and/or positive APOE4 alleles.
Masking: Double (Participant, Investigator)
Primary Purpose: Diagnostic
Official Title: 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
Actual Study Start Date : October 17, 2016
Actual Primary Completion Date : February 18, 2020
Actual Study Completion Date : February 21, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Prodromal AD (MCI)

Altoida: neuropsychological, MRI, EEG and CSF biomarkers

MCI participants will undergo at baseline and every 6 months a neurological examination and a neuropsychological assessment. Alzheimer disease biomarkers' measurements will be performed at inclusion and at the end of the study (or the conversion).

Other: Altoida: neuropsychological, MRI, EEG and CSF biomarkers

Data collection at baseline: clinical (neurological, activity of the daily life, instrumental activity of the daily life, depression scale), standard neuropsychological exam, ALTOIDA and neurophysiology (EEG/ERPs) in both Prodromal and Preclinical AD subjects. In both Prodromal and Preclinical AD subjects, APOE genotyping. The local clinical Unit should document the positivity at the baseline session of at least one of the biomarkers of AD mentioned above.

Data collection at 6, 12, 24 and 36 months of follow up: clinical (neurological, activity of the daily life, instrumental activity of the daily life, depression scale), standard neuropsychological exam, ALTOIDA and neurophysiology (EEG/ERPs) in both Prodromal and Preclinical AD subjects.


Experimental: Preclinical AD (cognitively normal)

Altoida: neuropsychological, MRI, EEG and CSF biomarkers

Cognitively normal participants at risk will undergo at baseline and every 6 months a neurological examination and a neuropsychological assessment. Alzheimer disease biomarkers' measurements will be performed at inclusion and at the end of the study (or the conversion).

Other: Altoida: neuropsychological, MRI, EEG and CSF biomarkers

Data collection at baseline: clinical (neurological, activity of the daily life, instrumental activity of the daily life, depression scale), standard neuropsychological exam, ALTOIDA and neurophysiology (EEG/ERPs) in both Prodromal and Preclinical AD subjects. In both Prodromal and Preclinical AD subjects, APOE genotyping. The local clinical Unit should document the positivity at the baseline session of at least one of the biomarkers of AD mentioned above.

Data collection at 6, 12, 24 and 36 months of follow up: clinical (neurological, activity of the daily life, instrumental activity of the daily life, depression scale), standard neuropsychological exam, ALTOIDA and neurophysiology (EEG/ERPs) in both Prodromal and Preclinical AD subjects.





Primary Outcome Measures :
  1. Change in sensitivity , specificity and accuracy of Altoida models [ Time Frame: baseline, 6, 12, 24, 36 and 42 months of 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.


Secondary Outcome Measures :
  1. Change from Baseline in Clinical Measure 1 [ Time Frame: baseline, 6, 12, 24, 36 and 42 months of follow up ]
    Clinical Dementia Rating (CDR), including CDR sum of boxes (CDR-SB) and clinician's diagnostic assessment

  2. Change from Baseline in Clinical Measure 2 [ Time Frame: baseline, 6, 12, 24, 36 and 42 months of follow up ]
    Geriatric Depression Scale (GDS)

  3. Change from Baseline in Clinical Measure 3 [ Time Frame: baseline, 6, 12, 24, 36 and 42 months of follow up ]
    Functional Assessment Questionnaire (FAQ)

  4. Change from Baseline in Clinical Measure 4 [ Time Frame: baseline, 6, 12, 24, 36 and 42 months of follow up ]
    Mini Mental Status Exam (MMSE)

  5. Change from Baseline in Clinical Measure 5 [ Time Frame: baseline, 6, 12, 24, 36 and 42 months of follow up ]
    Neuropsychiatric Inventory Questionnaire (NPI-Q)

  6. Change from Baseline in Clinical Measure 6 [ Time Frame: baseline, 6, 12, 24, 36 and 42 months of follow up ]
    Activities of the daily life (ADL)

  7. Change from Baseline in Clinical Measure 7 [ Time Frame: baseline, 6, 12, 24, 36 and 42 months of follow up ]
    Instrumental activities of the daily life (iADL)

  8. Change from Baseline in Cognitive Measure [ Time Frame: baseline, 6, 12, 24, 36 and 42 months of follow up ]
    ADAS Cog

  9. Change from Baseline in Cognitive Measure [ Time Frame: baseline, 6, 12, 24, 36 and 42 months of follow up ]
    -Rey-Osterrieth Complex Figure Test (Copy)

  10. Change from Baseline in Cognitive Measure [ Time Frame: baseline, 6, 12, 24, 36 and 42 months of follow up ]
    Trail Making Test

  11. Change from Baseline in Cognitive Measure [ Time Frame: baseline, 6, 12, 24, 36 and 42 months of follow up ]
    Digit Span Forward

  12. Change from Baseline in Cognitive Measure [ Time Frame: baseline, 6, 12, 24, 36 and 42 months of follow up ]
    Category Fluency (Animals & Vegetables)

  13. Change from Baseline in Cognitive Measure [ Time Frame: baseline, 6, 12, 24, 36 and 42 months of follow up ]
    Digit Span Backward

  14. Change from Baseline in Cognitive Measure [ Time Frame: baseline, 6, 12, 24, 36 and 42 months of follow up ]
    Rey Osterrieth Complex Figure Test (30 minute delay)

  15. Change from Baseline in Cognitive Measure [ Time Frame: baseline, 6, 12, 24, 36 and 42 months of follow up ]
    Wechsler Memory Scale - Revised (WMS-R) Digit Span

  16. Change from Baseline in Cognitive Measure [ Time Frame: baseline, 6, 12, 24, 36 and 42 months of follow up ]
    Wechsler Memory Scale Logical Memory

  17. Change from Baseline in Cognitive Measure [ Time Frame: baseline, 6, 12, 24, 36 and 42 months of follow up ]
    Wechsler Memory Scale Paragraph Memory (Immediate & Delayed Recall)

  18. Change from Baseline in Cognitive Measure [ Time Frame: baseline, 6, 12, 24, 36 and 42 months of follow up ]
    Wechsler Adult Intelligence Scale - Revised (WAIS-R) Digit-Symbol Substitution Test

  19. Change from Baseline in Cognitive Measure [ Time Frame: baseline, 6, 12, 24, 36 and 42 months of follow up ]
    Rey Auditory Verbal Learning Test (RAVLT)

  20. Secondary resting state EEG endpoints [ Time Frame: baseline, 6, 12, 24, 36 and 42 months of follow up ]
    EEG endpoints (occipital, parietal, and temporal sources of delta and low-frequency alpha rhythms) according to the PharmaCog WP5 European ADNI. These markers are expected to be related to disease status at baseline assessment and disease progression at follow-ups. Exploratory probability level of p < 0.05.

  21. Secondary resting state auditory oddball ERP endpoints [ Time Frame: baseline, 6, 12, 24, 36 and 42 months of follow up ]
    ERP endpoints (latency of scalp parietal P3b peak and activity of the cingulate and temporal-parietal sources of P3b peak according to PharmaCog WP5 European ADNI). These markers are expected to be related to disease status at baseline assessment and disease progression at follow-ups. Exploratory probability level of p < 0.05.

  22. Total Abeta 1-42 (Aβ42) amyloid deposition [ Time Frame: baseline, 6, 12, 24, 36 and 42 months of follow up ]
    Currently available evidence strongly supports the position that the initiating event in Alzheimer's disease (AD) is related to abnormal processing of beta-amyloid (Abeta) peptide, ultimately leading to formation of Abeta plaques in the brain. Baseline amount of CSF Abeta(42) will be investigated.

  23. Change of brain amyloid deposition [ Time Frame: baseline, 6, 12, 24, 36 and 42 months of follow up ]
    Biomarkers of brain beta-amyloidosis are reductions in CSF Abeta(42) and increased amyloid PET tracer retention. The change in amyloid deposition as measured by Abeta 1-42 (Aβ42) and its relation to the genetic, clinical, neuropsychological, EEG and ERP endpoints measurement will be assessed.

  24. Change of CSF biomarkers tau and ptau181 values [ Time Frame: baseline, 6, 12, 24, 36 and 42 months of follow up ]
    The change in CSF biomarkers tau and ptau181 values and its relation to the genetic, clinical, neuropsychological, EEG and ERP endpoints measurement will be assessed.

  25. MRI (Optional) [ Time Frame: baseline, 6, 12, 24, 36 and 42 months of follow up ]
    Relationship between MRI measures (brain volume, hippocampus atrophy, vascular lesions) and biomarkers.

  26. Changes in Driving breaking force [ Time Frame: baseline, 6, 12, 24, 36 and 42 months of follow up ]
    Changes in driving behavior, such as breaking force observed continuesly through in-car sensors or dongles.

  27. Changes in Driving acceleration velocity [ Time Frame: baseline, 6, 12, 24, 36 and 42 months of follow up ]
    Changes in driving behavior, such as acceleration velocity observed continuesly through in-car sensors or dongles.

  28. Changes in Driving direction [ Time Frame: baseline, 6, 12, 24, 36 and 42 months of follow up ]
    Changes in driving behavior, such as sudden changes of direction observed continuesly through in-car sensors or dongles.

  29. Changes in driving violations [ Time Frame: Continuous measurement for 42 months ]
    Changes in driving behavior, such as speed limit violations observed continuesly through in-car sensors or dongles.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   55 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02843529


Sponsors and Collaborators
Altoida
Greek Alzheimer's Association and Related Disorders
University of Roma La Sapienza
IRCCS Centro San Giovanni di Dio Fatebenefratelli
Neuromed IRCCS
Scripps Health
Global Brain Health Institute (GBHI)
Takeda Pharmaceuticals International, Inc.
Research Center on Computational Biomarkers (RCCBM)
BiHELab - Bioinformatics and Human Electrophysiology Lab
Fundacion Clinic per a la Recerca Biomédica
University of Dublin, Trinity College
University of Barcelona
EIT Health
Klinik Hirslanden, Zurich
Center for BrainHealth - The University of Texas at Dallas
Investigators
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Study Chair: Mark Wiederhold, PhD Scripps Clinic La Jolla Poole Building
Additional Information:
Publications:

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Responsible Party: Altoida
ClinicalTrials.gov Identifier: NCT02843529    
Other Study ID Numbers: altoidaML01
First Posted: July 26, 2016    Key Record Dates
Last Update Posted: May 27, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: neuromotor data sharing
Keywords provided by Altoida:
biomarkers
CSF
EEG
MRI
Digital biomarkers
Additional relevant MeSH terms:
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Alzheimer Disease
Memory Disorders
Asymptomatic Diseases
Cognitive Dysfunction
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Cognition Disorders
Neurobehavioral Manifestations
Neurologic Manifestations
Signs and Symptoms
Disease Attributes
Pathologic Processes