PROSA—a multicenter prospective observational study to develop low-burden digital speech biomarkers in ALS and FTD

Abstract

Objective

There is a need for novel biomarkers that can indicate disease state, project disease progression, or assess response to treatment for amyotrophic lateral sclerosis (ALS) and associated neurodegenerative diseases such as frontotemporal dementia (FTD). Digital biomarkers are especially promising as they can be collected non-invasively and at low burden for patients. Speech biomarkers have the potential to objectively measure cognitive, motor as well as respiratory symptoms at low-cost and in a remote fashion using widely available technology such as telephone calls.

Methods

The PROSA study aims to develop and evaluate low-burden frequent prognostic digital speech biomarkers. The main goal is to create a single, easy-to-perform battery that serves as a valid and reliable proxy for cognitive, respiratory, and motor domains in ALS and FTD. The study will be a multicenter 12-months observational study aiming to include 75 ALS and 75 FTD patients as well as 50 healthy controls and build on three established longitudinal cohorts: DANCER, DESCRIBE-ALS and DESCRIBE-FTD. In addition to the extensive clinical phenotyping in DESCRIBE, PROSA collects a comprehensive speech protocol in fully remote and automated fashion over the telephone at four time points. This longitudinal speech data, together with gold standard measures, will allow advanced speech analysis using artificial intelligence for the development of speech-based phenotypes of ALS and FTD patients measuring cognitive, motor and respiratory symptoms.

Conclusion

Speech-based phenotypes can be used to develop diagnostic and prognostic models predicting clinical change. Results are expected to have implications for future clinical trial stratification as well as supporting innovative trial designs in ALS and FTD.

Keywords:

• Speech biomarkers
• digital biomarkers
• ALS
• FTD
• multicenter observational study

Author contributions

JT wrote the manuscript and created the figures. JB, EB, EK, MK, NL, JR, SS, AS and AH assisted with writing the manuscript. AH and AS are principal investigators for DZNE in PROSA and gave input about disease background and cohorts. EK and MK co-designed the telephone assessment, JB, EB, MK, AH and AS managed ethic approvals. All authors have read and approved the manuscript.

Declaration of interest

JT, EB, SS and NL are employees of the speech biomarker company ki:elements GmbH. JT and NL hold shares in the speech biomarker company ki:elements GmbH. JR is an employee of the speech biomarker company Winterlight Labs Inc. AH, AS, JB, EK, and MK report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Data availability statement

All data can be made available upon request. For requests, please contact DZNE PIs of PROSA AS or AH.

Additional information

Funding

This work is supported by the DZNE and received funding from the Target ALS Foundation, the Alzheimer's Drug Discovery Foundation Diagnostic Accelerator as well as Gates Ventures.