Diagnosis and Monitoring of Disease Progression Using Deep Neuro Signatures

Recruiting

• Conditions: Mild Cognitive Impairment; Alzheimer's Disease

• Registration Number: NCT05153941
• Lead Sponsor: Altoida

Brief Summary

Alzheimer's disease (AD) clinically characterized by the cognitive impairment and lowering of various functional abilities lead to staggering costs and suffering, which are particularly related to the social impacts of caring for increasingly disabled individuals. Some of these changes can be almost undetectable in the early stages of the disease, worsening over time often and at a varying rate of progression in different people. The traditional clinical scales or questionnaires such as ADCS (Alzheimer's Disease Cooperative Study) - ADL (Activities of Daily Living) for detecting such functional disabilities are typically blunt and rely on direct observation or caregiver recall. Digital technologies, particularly those based on the use of smart phones, wearable and/or home-based monitoring devices, here defined as 'Remote Measurement Technologies' (RMTs), provide an opportunity to change radically the way in which functional assessment is undertaken in AD, RMTs have potential to obtain better measurements of behavioral and biological parameters associated with individual Activities of Daily Living (ADL) when compared to the current subjective scales or questionnaires. Divergence from normative ADL profiles could objectively indicate the presence of incipient functional impairment at the very early stages of AD. Therefore, the main hypothesis of this study is that RMTs should allow the detection of impairments in functional components of ADLs that occur below the detection threshold of clinical scale or questionnaires.

Detailed Description

Relevant outcome measurements for the study have been selected through the following longitudinal process:

Identification of functional domains that meet one or more of the following criteria:

Predicts conversion of MCI due to AD to mild AD dementia. Impaired in mild AD dementia. Predicts functional decline in AD dementia. Reported as important by an AD dementia patient advisory board. Identification of candidate RMTs to cover real-life measurement of the functional domains identified in step 1.

Identification of candidate digital biomarkers, which are life-log data such as steps, sleep, heart rate and exercise collected by RMTs, to cover clinical measurement of the functional domains identified in step 1.

Functional domains, RMTs, and clinical assessments that resulted from the selection process above are listed in Table 1, and 2. The selection process described in step 1 resulted in the identification of the following functional domains, sorted by relevance \[HR (highly relevant), R (relevant), N (neutral), and LR (least relevant)\].

The central assumption of the study is that functional disabilities proportionally increase with the progressive worsening of the AD. A recent classification proposed by the FDA 2018 draft guidance for the development of novel treatments in AD identifies the early disease progression in 3 stages: (a) Patients with characteristic pathophysiologic changes of Preclinical AD but no evidence of clinical impact (Stage 1) (b) Patients with characteristic pathophysiologic changes of AD and subtle or more apparent detectable abnormalities on sensitive neuropsychological measures, but no functional impairment (Stage 2), and (c) Patients with characteristic pathophysiologic changes of AD and subtle or more apparent detectable abnormalities on sensitive neuropsychological measures, but mild and detectable functional impairment (Stage 3). The aim of the DNS study is to assess the feasibility, utility and performance of selected RMTs in profiling ADL in real-world settings. This goal will be achieved by evaluating digital signals collected either continuously, or daily, or weekly at home, either using wearable devices or home-located ambient devices, determining as much as possible the specific context-dependent conditions in which the signals are measured. As a general hypothesis, RMTs will deliver more sensitive and less variable measurements when compared to standard clinical assessments, questionnaires and tests measuring specific functional capabilities in the clinics.

The most important results of the study will be (1) the evidence that some RMT parameters will provide insights for lower variance than the standard scales or questionnaires, (2) the capacity of Altoida, Inc. NMI and/or RMTs to significantly differentiate the preclinical AD stages 1 \& 2 when compared to healthy volunteers with negative AD biomarkers as a control, and (3) a similar capabilities of Altoida, Inc. NMI and/or RMTs to detect monotonic change in the mild cognitive impairment (MCI) due to AD group and, even more, in mild, moderate and severe AD dementia groups, proportional to the specific functional impairment known to worsen during the disease progression.

Study Timeline

• Study First Submitted: 2021-11-30
• Study First Submitted QC: 2021-11-30
• Study First Posted: 2021-12-10
• Study Start: 2022-01-31
• Status Verified: 2023-09
• Last Update Submitted: 2023-09-28
• Last Update Posted: 2023-09-29
• Primary Completion: 2029-01-31
• Study Completion: 2030-01-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 3500

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Demographics, medical history, physical status, life-habits, and medication from the analysis of neuropsychological assessments.	5 years	Assess statistically significant difference between healthy volunteers, preclinical AD, MCI due to AD, mild, moderate and severe AD dementia focusing on their demographics, medical history, physical status, life-habits, and medication from the analysis of neuropsychological assessments.
ADL using selected RMTs	5 years	Assess statistically significant difference between healthy volunteers, preclinical AD, MCI due to AD, mild, moderate and severe AD dementia in outcome measures of ADL using selected RMTs.
Neuropsychological assessment like Altoida, Inc. Neuro Motor Index (NMI) medical device	5 years	Assess statistically significant difference between healthy volunteers, preclinical AD, MCI due to AD, mild, moderate and severe AD dementia using RMTs, neuropsychological assessment like the Altoida, Inc. Neuro Motor Index (NMI) medical device.
Demographics, medical history, physical status, life-habits, and medication from the analysis of RMTs	5 years	Assess statistically significant difference between healthy volunteers, preclinical AD, MCI due to AD, mild, moderate and severe AD dementia focusing on their demographics, medical history, physical status, life-habits, and medication from the analysis of RMTs.
Neuropsychological assessment like the Clinical Dementia Rating (CDR) scale	5 years	Assess statistically significant difference between healthy volunteers, preclinical AD, MCI due to AD, mild, moderate and severe AD dementia using RMTs, neuropsychological assessment like CDR.
Demographics, medical history, physical status, life-habits, and medication from the analysis of biomarker measurements.	5 years	Assess statistically significant difference between healthy volunteers, preclinical AD, MCI due to AD, mild, moderate and severe AD dementia focusing on their demographics, medical history, physical status, life-habits, and medication from the analysis of biomarker measurements.
Demographics, medical history, physical status, life-habits, and medication from the analysis of Altoida NMI medical device.	5 years	Assess statistically significant difference between healthy volunteers, preclinical AD, MCI due to AD, mild, moderate and severe AD dementia focusing on their demographics, medical history, physical status, life-habits, and medication from the analysis of Altoida NMI medical device.

Trial Locations

Locations (1)

Nikaia Ag Panteleimon Hospital; 🇬🇷 Athens, Greece