FUTURE-US: Amyloid Prediction in Early Stage Alzheimer's Disease Through Speech Phenotyping - FUTURE Extension

Sponsor

Novoic Limited (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04951284

Collaborator

(none)

Enrollment

Location

42.8

Anticipated Duration (Months)

1.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary objective of the study is to evaluate whether a set of algorithms analysing acoustic and linguistic patterns of speech, can predict change in Preclinical Alzheimer's Clinical Composite with semantic processing (PACC5) between baseline and +12 month follow up across all four Arms, as measured by the coefficient of individual agreement (CIA) between the change in PACC5 and the corresponding regression model, trained on baseline speech data to predict it. Secondary objectives include (1) evaluating whether similar algorithms can predict change in PACC5 between baseline and +12 month follow up in the cognitively normal (CN) and MCI populations separately; (2) evaluating whether similar algorithms trained to regress against PACC5 scores at baseline, still regress significantly against PACC5 scores at +12 month follow-up, as measured by the coefficient of individual agreement (CIA) between the PACC5 composite at +12 months and the regression model, trained on baseline speech data to predict PACC5 scores at baseline; (3) evaluating whether similar algorithms can classify converters vs non-converters in the cognitively normal Arms (Arm 3 + 4), and fast vs slow decliners in the MCI Arms (Arm 1 + 2), as measured by the Area Under the Curve (AUC) of the receiver operating characteristic curve, sensitivity, specificity and Cohen's kappa of the corresponding binary classifiers. Secondary objectives include the objectives above, but using time points of +24 months and +36 months; and finally to evaluate whether the model performance for the objectives and outcomes above improved if the model has access to speech data at 1 week, 1 month, and 3 month timepoints.

Condition or Disease	Intervention/Treatment	Phase
Alzheimer Disease Preclinical Alzheimer's Disease Prodromal Alzheimer's Disease Alzheimer's Disease (Incl Subtypes) Mild Cognitive Impairment

Study Design

Study Type:

Observational [Patient Registry]

Anticipated Enrollment :

50 participants

Observational Model:

Case-Control

Time Perspective:

Prospective

Official Title:

A Study to Evaluate the Ability of Speech- and Language-based Digital Biomarkers to Detect and Characterise Prodromal and Preclinical Alzheimer's Disease in a Clinical Setting - AMYPRED-US FUTURE Extension Study.

Actual Study Start Date :

Jan 21, 2021

Anticipated Primary Completion Date :

Aug 15, 2022

Anticipated Study Completion Date :

Aug 15, 2024

Arms and Interventions

Arm	Intervention/Treatment
Arm 1: MCI amyloid positive Meet the National Institute of Aging - Alzheimer's Association (NIA-AA) core clinical criteria (2011) for MCI due to Alzheimer's Positive amyloid PET or amyloid CSF status. MMSE 23-30 (inclusive)
Arm 2: MCI amyloid negative Non-AD Mild Cognitive Impairment (MCI) Negative amyloid PET or amyloid CSF status. MMSE 23-30 (inclusive)
Arm 3: CN amyloid positive Absence of a diagnosis of cognitive disorder and/or subjectively reported cognitive decline Positive amyloid PET or amyloid CSF status. MMSE 26-30 (inclusive)
Arm 4: CN amyloid negative Absence of a diagnosis of cognitive disorder and/or subjectively reported cognitive decline Negative amyloid PET or amyloid CSF status. MMSE 26-30 (inclusive)

Outcome Measures

Primary Outcome Measures

The agreement between the change in the PACC5 composite between baseline and +12 months and the corresponding regression model, trained on baseline speech data, predicting in all four Arms, as measured by the coefficient of individual agreement (CIA). [12 months]

Secondary Outcome Measures

The agreement between the change in the PACC5 composite between baseline and +24 months and the corresponding regression model, trained on baseline speech data, predicting in all four Arms, as measured by the coefficient of individual agreement (CIA). [24 months]
The agreement between the change in the PACC5 composite between baseline and +36 months and the corresponding regression model, trained on baseline speech data, predicting in all four Arms, as measured by the coefficient of individual agreement (CIA). [36 months]
The agreement between the change in the PACC5 composite between baseline and +12 months and the corresponding regression model, trained on baseline speech data, to predict it in the CN Arms (Arms 3 and 4), as measured by the CIA. [12 months]
The agreement between the change in the PACC5 composite between baseline and +24 months and the corresponding regression model, trained on baseline speech data, to predict it in the CN Arms (Arms 3 and 4), as measured by the CIA. [24 months]
The agreement between the change in the PACC5 composite between baseline and +36 months and the corresponding regression model, trained on baseline speech data, predicting it in the MCI Arms (Arms 1 and 2), as measured by the CIA. [36 months]
The agreement between the PACC5 composite at +12 months and the corresponding regression model, trained on baseline speech data, predicting in all four Arms based on +12 month speech data, as measured by the coefficient of individual agreement (CIA). [12 months]
The agreement between the PACC5 composite at +24 months and the corresponding regression model, trained on baseline speech data, predicting in all four Arms based on +12 month speech data, as measured by the coefficient of individual agreement (CIA). [24 months]
The agreement between the PACC5 composite at +36 months and the corresponding regression model, trained on baseline speech data, predicting in all four Arms based on +12 month speech data, as measured by the coefficient of individual agreement (CIA). [36 months]
The agreement between the PACC5 composite and the corresponding regression model, trained on baseline speech data and +12 month speech data, as measured by the coefficient of individual agreement (CIA). [12 months]
The agreement between the PACC5 composite and the corresponding regression model, trained on baseline speech data and +24 month speech data, as measured by the coefficient of individual agreement (CIA). [24 months]
The agreement between the PACC5 composite and the corresponding regression model, trained on baseline speech data and +36 month speech data, as measured by the coefficient of individual agreement (CIA). [36 months]
The AUC of the binary classifier distinguishing between converters vs non-converters in the cognitively normal (CN) Arms (Arms 3 and 4); converters defined as having a CDR Global score of 0.5 or more at +12 months. [12 months]
The AUC of the binary classifier distinguishing between converters vs non-converters in the cognitively normal (CN) Arms (Arms 3 and 4); converters defined as having a CDR Global score of 0.5 or more at +24 months. [24 months]
The AUC of the binary classifier distinguishing between converters vs non-converters in the cognitively normal (CN) Arms (Arms 3 and 4); converters defined as having a CDR Global score of 0.5 or more at +36 months. [36 months]
The sensitivity of the binary classifier distinguishing between converters vs non-converters in the cognitively normal (CN) Arms (Arms 3 and 4); converters defined as having a CDR Global score of 0.5 or more at +12 months. [12 months]
The sensitivity of the binary classifier distinguishing between converters vs non-converters in the cognitively normal (CN) Arms (Arms 3 and 4); converters defined as having a CDR Global score of 0.5 or more at +24 months. [24 months]
The sensitivity of the binary classifier distinguishing between converters vs non-converters in the cognitively normal (CN) Arms (Arms 3 and 4); converters defined as having a CDR Global score of 0.5 or more at +36 months. [36 months]
The specificity of the binary classifier distinguishing between converters vs non-converters in the cognitively normal (CN) Arms (Arms 3 and 4); converters defined as having a CDR Global score of 0.5 or more at +12 months. [12 months]
The specificity of the binary classifier distinguishing between converters vs non-converters in the cognitively normal (CN) Arms (Arms 3 and 4); converters defined as having a CDR Global score of 0.5 or more at +24 months. [24 months]
The specificity of the binary classifier distinguishing between converters vs non-converters in the cognitively normal (CN) Arms (Arms 3 and 4); converters defined as having a CDR Global score of 0.5 or more at +36 months. [36 months]
The Cohen's kappa of the binary classifier distinguishing between converters vs non-converters in the cognitively normal (CN) Arms (Arms 3 and 4); converters defined as having a CDR Global score of 0.5 or more at +12 months. [12 months]
The Cohen's kappa of the binary classifier distinguishing between converters vs non-converters in the cognitively normal (CN) Arms (Arms 3 and 4); converters defined as having a CDR Global score of 0.5 or more at +24 months. [24 months]
The Cohen's kappa of the binary classifier distinguishing between converters vs non-converters in the cognitively normal (CN) Arms (Arms 3 and 4); converters defined as having a CDR Global score of 0.5 or more at +36 months. [36 months]
The AUC of the binary classifier distinguishing between fast decliners vs slow decliners in the MCI Arms (Arms 1 and 2) at +12 months. [12 months]
The AUC of the binary classifier distinguishing between fast decliners vs slow decliners in the MCI Arms (Arms 1 and 2) at +24 months. [24 months]
The AUC of the binary classifier distinguishing between fast decliners vs slow decliners in the MCI Arms (Arms 1 and 2) at +36 months. [36 months]
The sensitivity of the binary classifier distinguishing between fast decliners vs slow decliners in the MCI Arms (Arms 1 and 2) at +12 months. [12 months]
The sensitivity of the binary classifier distinguishing between fast decliners vs slow decliners in the MCI Arms (Arms 1 and 2) at +24 months. [24 months]
The sensitivity of the binary classifier distinguishing between fast decliners vs slow decliners in the MCI Arms (Arms 1 and 2) at +36 months. [36 months]
The specificity of the binary classifier distinguishing between fast decliners vs slow decliners in the MCI Arms (Arms 1 and 2) at +12 months. [12 months]
The specificity of the binary classifier distinguishing between fast decliners vs slow decliners in the MCI Arms (Arms 1 and 2) at +24 months. [24 months]
The specificity of the binary classifier distinguishing between fast decliners vs slow decliners in the MCI Arms (Arms 1 and 2) at +36 months. [36 months]
The Cohen's kappa of the binary classifier distinguishing between fast decliners vs slow decliners in the MCI Arms (Arms 1 and 2) at +12 months. [12 months]
The Cohen's kappa of the binary classifier distinguishing between fast decliners vs slow decliners in the MCI Arms (Arms 1 and 2) at +24 months. [24 months]
The Cohen's kappa of the binary classifier distinguishing between fast decliners vs slow decliners in the MCI Arms (Arms 1 and 2) at +36 months. [36 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Subjects are fully eligible for and have completed the AMYPRED-US (Amyloid Prediction in early stage Alzheimer's disease from acoustic and linguistic patterns of speech) study.

(See https://clinicaltrials.gov/ct2/show/NCT04928976)