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

Sponsor

Novoic Limited (Industry)

Overall Status

Completed

CT.gov ID

NCT04928976

Collaborator

(none)

Enrollment

Location

6.2

Actual Duration (Months)

10.8

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 detect amyloid-specific cognitive impairment in early stage Alzheimer's disease, as measured by the AUC of the receiver operating characteristic (ROC) curve of the binary classifier distinguishing between amyloid positive (Arms 1 and 3) and amyloid negative (Arms 2 and 4) Arms. Secondary objectives include (1) evaluating whether similar algorithms can detect amyloid-specific cognitive impairment in the cognitively normal (CN) and MCI Arms respectively, as measured on binary classifier performance; (2) whether they can detect MCI, as measured on binary classifier performance (AUC, sensitivity, specificity, Cohen's kappa), and the agreement between the PACC5 composite and the corresponding regression model predicting it in all Arms pooled (Wilcoxon signed-rank test, CIA); (3) evaluating variables that can impact performance of such algorithms of covariates from the speaker (age, gender, education level) and environment (measures of acoustic quality).

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]

Actual Enrollment :

67 participants

Observational Model:

Case-Control

Time Perspective:

Cross-Sectional

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

Actual Study Start Date :

Jan 22, 2021

Actual Primary Completion Date :

Jul 30, 2021

Actual Study Completion Date :

Jul 30, 2021

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

Area under the curve (AUC) of the receiver operating characteristic (ROC) curve of the binary classifier distinguishing between amyloid positive (Arms 1 and 3) and amyloid negative (Arms 2 and 4) Arms using speech recordings as input. [baseline]

Secondary Outcome Measures

The sensitivity of the binary classifier distinguishing between amyloid positive (Arms 1 and 3) and amyloid negative (Arms 2 and 4) Arms. [baseline]
The specificity of the binary classifier distinguishing between amyloid positive (Arms 1 and 3) and amyloid negative (Arms 2 and 4) Arms. [baseline]
The Cohen's kappa of the binary classifier distinguishing between amyloid positive (Arms 1 and 3) and amyloid negative (Arms 2 and 4) Arms. [baseline]
The sensitivity of the binary classifier distinguishing between amyloid positive cognitively normal (CN) (Arm 3) and amyloid negative cognitively normal (CN) (Arm 4) Arms. [baseline]
The specificity of the binary classifier distinguishing between amyloid positive cognitively normal (CN) (Arm 3) and amyloid negative cognitively normal (CN) (Arm 4) Arms. [baseline]
The Cohen's kappa of the binary classifier distinguishing between amyloid positive cognitively normal (CN) (Arm 3) and amyloid negative cognitively normal (CN) (Arm 4) Arms. [baseline]
The AUC of the binary classifier distinguishing between amyloid positive cognitively normal (CN) (Arm 3) and amyloid negative cognitively normal (CN) (Arm 4) Arms. [baseline]
The sensitivity of the binary classifier distinguishing between amyloid positive MCI (Arm 1) and amyloid negative MCI (Arm 2) Arms. [baseline]
The specificity of the binary classifier distinguishing between amyloid positive MCI (Arm 1) and amyloid negative MCI (Arm 2) Arms. [baseline]
The Cohen's kappa of the binary classifier distinguishing between amyloid positive MCI (Arm 1) and amyloid negative MCI (Arm 2) Arms. [baseline]
The AUC of the binary classifier distinguishing between amyloid positive MCI (Arm 1) and amyloid negative MCI (Arm 2) Arms. [baseline]
The sensitivity of the binary classifier distinguishing between the MCI (Arms 1 and 2) and the CN (Arms 3 and 4) Arms. [baseline]
The specificity of the binary classifier distinguishing between the MCI (Arms 1 and 2) and the CN (Arms 3 and 4) Arms. [baseline]
The Cohen's kappa of the binary classifier distinguishing between the MCI (Arms 1 and 2) and the CN (Arms 3 and 4) Arms. [baseline]
The AUC of the binary classifier distinguishing between the MCI (Arms 1 and 2) and the CN (Arms 3 and 4) Arms. [baseline]
The agreement between the PACC5 composite and the corresponding regression model predicting it in all four Arms, as measured by the coefficient of individual agreement (CIA). [baseline]
For each classifier/regressor in outcome 1-16, the correlation between the AUC/CIA and each age group, gender and speech-to-reverberation modulation energy ratio group, as measured by the Kendall rank correlation coefficient. [baseline]

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Amyloid status must be known, based on an amyloid PET scan or CSF amyloid test, no older than 30 months at the time of consent for Arm 2 and Arm 4 participants (amyloid negative Arms).
Amyloid status must be known, based on an amyloid PET scan or CSF amyloid test, no older than 60 months at the time of consent for Arm 1 and Arm 3 (amyloid positive Arms).
Subjects must be aged 50-85 (inclusive).
Subjects must have MMSE scores of 23-30 (inclusive) based on a test not older than 1 month at the time of the visit.
Date of diagnosis (if applicable) maximum of five years prior to consent.
Subjects' first language must be English.
Willing to participate in a study investigating speech and dementia.
Availability of a person ('caregiver') who in the investigator's judgment has frequent and sufficient in-person contact with the participant, and is able to provide accurate information regarding the participant's cognitive and functional abilities. This is most likely met when living with a caregiver.
Able to provide valid informed consent.
Able to use, or has a caregiver who is able to use a smartphone device.
Has access to a smartphone device running an operation system of Android 6 or above; or iOS 10 or above.

If taking part in the study through virtual visits, the following inclusion criteria also applies:

Able to use, or has a caregiver who is able to use a personal computer, notebook or tablet.
Has access to a personal computing device of that is:
Running an operating system of macOS X with macOS 10.9 or later; or Windows 7 or above; or Ubuntu 12.04 or higher; or
Have access to one of following internet browser software Internet Explorer version 11 or above; or Microsoft Edge version 12 or above; or Firefox version 27 or above; or Google Chrome version 30 or above; or Safari version 7 or above; capable of audio and video recording; and able to connect to the internet.

Exclusion Criteria:

Clinically significant unstable psychiatric illness in 6 months.
Diagnosis of General Anxiety Disorder.
Current, or history within the past 2 years of major depressive disorder diagnosis (according to DSM-5 criteria); or psychiatric symptoms that, in the opinion of the investigator, could interfere with study procedures.
History or presence of stroke within the past 2 years.
Documented history of transient ischemic attack or unexplained loss of consciousness within the last 12 months.
The participant is using drugs to treat symptoms related to AD, and the doses of these drugs were not stable for at least 8 weeks prior to consent.