Clinical trial NCT06223438: Detecting an MCI and Amyloid Digital Neuro Signature(DNS) Using Altoida's Multimodal Digital Biomarkers.
Official title: Detecting an MCI and Amyloid Digital Neuro Signature(DNS) Using Altoida's Multimodal Digital Biomarkers.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Alzheimer Disease
MCI
Keywords: Augmented reality
Machine learning
MCI
Amyloid pathology
Alzheimer's disease
biomarkers
diagnosis
Lead sponsor: Altoida
Sponsor class: INDUSTRY
First posted: 2024-01-25
Enrollment: 614
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Participants will be identified as cognitively unimpaired or with MCI by a clinical diagnosis with defined adjudication criteria. For biomarker status determination, participants can be enrolled with a historical positive amyloid status assessment result through CSF analysis or amyloid-PET testing up to 18 months before the Altoida assessment. Historical amyloid negative data can be accepted up to 6-12 months before the Altoida assessment if MMSE\>26. There will be at least 668 participants (334 CN; 334 MCI) (50+ years), enrolled globally across approximately six sites balanced for amyloid status (positive/negative). Underrepresented populations will be targeted with the goal of also maintaining an equal balance of males and females.

Brief summary: The purpose of this study is to establish multiple points of clinical validity for the Altoida digital biomarker assessment in individuals with a clinical diagnosis of cognitively normal (CN) and Mild Cognitive Impairment (MCI). Participants will use the Altoida app and the de-identified sensor data captured by the device will be used to train specific machine-learning algorithms to recognize early symptoms of cognitive decline, such as MCI or MCI with likelihood of amyloid pathology, as measured by digital biomarkers (T1 - Visit 1). Participants will be invited for an additional visit to evaluate test-retest reliability (T1' - Visit 2). Optionally, an updated variation of the Altoida app will be tested over the course of two additional visits to ensure optimal digital assessment delivery based on best practices in neuropsychological testing, user experience design, and data collection integrity (T2 - Visit 3 and T2' - Visit 4).

Detailed description: Digital biomarkers are indicators of a person's health status as measured by a digital device. They are gaining traction in neurology research for their capacity to offer accurate, accessible, and continuous measures of cognitive performance that could enable earlier diagnoses. For individuals at risk of developing dementia, early and differential diagnosis is key to streamlining patient management, benefiting patients and healthcare systems alike.

While conventional neuropsychological assessments remain the gold standard for assessing cognitive and functional decline, these evaluations are lengthy (90-120 min), require a trained specialist, and are not free of bias and practice effects. In this context, digital biomarkers that enable the continuous and objective evaluation of multidimensional features assessing activities of daily living may have the potential to capture subtle changes in cognition and functional ability before the onset of cognitive decline.

The Altoida Digital Biomarker Platform enables an objective evaluation of an individual's cognitive and functional impairment. The Altoida platform consists of two parts: 1) a participant-facing assessment (tablet-based) and 2) a site-facing analytics and reporting web portal. The assessment evaluates cognitive and functional skills based on a series of motor and augmented reality (AR) tasks that mirror the engagement of the brain during activities of daily living (Figure 1). These activities include tapping and tracing shapes, as well as placing and finding virtual objects while faced with a distractor task. The assessment takes an average of 10 minutes (average cognitively normal) to 18 minutes (average MCI) to complete. The dashboard provides real-time analytics and integration of study data into clinical workflows. The platform is currently intended for investigational use only. It has not received FDA pre-marketing clearance or approval.

The platform evaluates multi-modal features, including micro-movements, speed, reaction times, and navigation trajectories, which are used to train specific machine-learning models, termed Digital Neuro Signature (DNS). Using machine learning, the digital biomarkers extracted by the Altoida assessment can be used to measure a patient's cognitive performance and to identify distinct clinical outcomes, such as MCI and MCI with likelihood of amyloid pathology in an ecological manner. The assessment also generates scores of specific brain domains of cognition defined by the DSM-V, such as learning and memory, executive function, complex attention, and perceptual-motor coordination derived from specific digital features scored with normative models (age and sex-adjusted). These are derived from specific digital features scored with normative models.

In previous studies, Altoida's digital biomarkers were found to be useful in detecting early cognitive decline and also in predicting progression to dementia. In recent years, the Altoida assessment has been used across several global research studies, confirming the ease of use, non-invasiveness, potential to identify cognitive impairment as well as correlations with neuropsychological assessments. Early clinical recognition of Alzheimer's disease (AD) is critical. There is currently no software-based tool approved by regulatory authorities to adjunctively diagnose individuals with MCI and amyloid positivity, which is a population with a greater likelihood of progressing to full AD dementia. Early and differential diagnosis could create opportunities for participation in clinical trials of disease-modifying therapies and assist drug developers with accelerating the enrollment of the right patients for the right therapies.

Eligibility criteria: Inclusion Criteria:

* Participants must provide written informed consent in the EC/IRB-approved informed consent form or have a Legally Authorized Representative (LAR) provide written consent on the participant's behalf;

  * Male or female, 50+ years at the time of consent;
  * Participants must be willing to comply with all study procedures as outlined in the informed consent;
  * Fluency in the language of the tests used at the study site;
  * At least four years of formal education (from primary school onwards);
  * Adequate vision to complete the Altoida assessment and neuropsychological tests with or without corrective lenses;
  * Have undisturbed locomotion;
  * Participants should have, when available, an amyloid status assessment result (positive or negative) through CSF analysis or amyloid-PET testing. Historical positive amyloid data is accepted up to 18 months before taking the Altoida assessment. Historical amyloid negative data can be accepted up to 6-12 months before the Altoida assessment if MMSE\>26. If historical amyloid data is unavailable, determining amyloid status will be an optional component of the study protocol. The decision to include this assessment and the specific method employed will be collaboratively discussed and decided upon between the study sponsor and the respective study site;
  * Optionally, participants might present, when available, a historical APOE, APP/PSEN1/2 genotype determination, and/or historical MRI/CT scan results relevant to clinical diagnosis.

Exclusion Criteria:

* ● Participants who have participated in a clinical trial longer than six months of any potential disease-modifying anti-amyloid AD treatment and remained active in the study for a duration of 6 or more months (i.e., continued receiving treatment);

  * Participants who, in the opinion of the Site Principal Investigator, have serious or unstable medical conditions that would prohibit their completion of all study procedures and data collection or that would preclude their participation;
  * Participants undergoing anticoagulant treatment or other blood dyscrasias, only if they need to undergo lumbar puncture for the assessment of amyloid pathology;
  * Participants with a history of stroke or seizures within one year of study start;
  * Participants with a history of chemotherapy within the past five years, or any type of malignancy or cancer that might interfere with the completion of the study, except for non-melanoma skin cancer or prostate cancer in situ;
  * Participants with restrictions of performing physical activities or who are not ambulatory;
  * Participants who have previously been enrolled in a study using the Altoida assessment

Primary outcomes:
measure: training and reinforcing a specific ML algorithm
timeFrame: 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Orlando
country: United States
facility: K2 Medical Research South Orlando
state: Florida
Study officials:
References:
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