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P4‐542: UTILITY OF SPEECH‐BASED DIGITAL BIOMARKERS FOR EVALUATING DISEASE PROGRESSION IN CLINICAL TRIALS OF ALZHEIMER'S DISEASE
Author(s) -
Simpson William,
Kaufman Liam,
Detke Mike,
Lynch Casey,
Butler Adam,
Dominy Steve
Publication year - 2019
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2019.08.089
Subject(s) - placebo , disease , biomarker , cohort , clinical trial , medicine , randomized controlled trial , cognition , psychology , audiology , oncology , pathology , psychiatry , biochemistry , chemistry , alternative medicine
Background: Recent clinical trials in Alzheimer’s disease have been overwhelmingly negative, spurring development of novel biomarkers which might capture changes in cognitive function with greater precision. Computational analysis of speech and language represent one such group of biomarkers(1,2). The objective of this study was to examine the utility of a speech-based digital biomarker for tracking disease progression and treatment response to investigational treatment COR388 in a group of patients with Alzheimer’s disease.Methods: The study was a small, double-blind placebo-controlled Phase 1b trial (NCT03418688) of COR388 with a cohort of nine (9) individuals with Alzheimer’s disease. Participants were randomized to receive COR388 or placebo in a 2:1 fashion, BID for 28 days. A tablet-based speech and language assessment was administered at Days 1, 15 and 28. Participants were asked to complete 2 picture description tasks and verbal responses were analyzed. Five aggregate markers, chosen for their previous association to AD(1,2), were computed: discourse, syntactic complexity, lexical complexity, information units and word finding difficulty (WFD). Results: Previous analysis of single outcomes showed significant improvement in the quality of picture descriptions for COR388 patients relative to placebo (increase in unique object content units, p1⁄40.016 and prepositions, p1⁄40.0011). Positive trends, but no significant differences in MMSE scores were observed(3). For aggregate markers, mean baseline to endpoint comparisons showed statistically significant (p<0.05) improvements in syntactic complexity, lexical complexity and information units in those treated with COR388. No significant within-subject differences were observed for placebo. Baseline to endpoint COR388 information unit differences remained significant post Bonferroni correction (p1⁄40.002). Between-group analysis of information unit change scores (Day 28 vs. Day 1) revealed a 10-point increase for COR388 vs. a 5-point change for placebo but this numerical difference was not significant (p1⁄40.21). Conclusions: In this preliminary trial, patients treated with COR388 showed signs of significant improvement relative to placebo as measured by a speech-based, digital biomarker. No significant changes in MMSE were observed suggesting that digital biomarkers may represent sensitive tools for tracking changes in cognition in small trials. The study also highlights the potential therapeutic benefit of COR388, though additional studies of sufficient power are needed.