Objective: To evaluate and establish the analytical validation, reliability, and meaningfulness of digital measures of gait and chorea in early Huntington’s disease (HD).

Background: HD is a neurodegenerative disease that manifests with gait changes and chorea, key markers of early disease that impact activities of daily living. Currently, clinical outcome assessments for HD rely on subjective, episodic, rater-administered assessments, generating a snapshot assessment that does not necessarily reflect patient functioning. Digital measures collected from wearable sensors may offer objective, sensitive, and remote assessments for clinical trials.

Method: MEND-HD is a FDA-funded, cross-sectional remote observational study. The study will enroll 40 participants with early HD (20 HD-ISS late-stage 2; 20 HD-ISS early-stage 3) and 20 controls. Participants will complete remote screening, baseline visits, and qualitative interviews. During the baseline visit, participants will perform mobility tasks while wearing wrist and trunk wearable sensors, which will be video-recorded for later annotation to support analytical validation. Assessments will include the virtual Unified Huntington Disease Rating Scale, patient reported outcomes measures, and standardized gait and mobility tasks. Participants will then wear the devices for 1-2 weeks at home to collect passive digital data on gait and chorea, physical activity, heart rate variability and sleep. We will use pre-trained large self-supervised machine learning models to measure daily living gait, including gait quality and quantity, and chorea. Test-retest reliability will be established across 2 weeks of testing and measures will be validated against established annotations and scales of disease severity. Participant and caregiver interviews will be conducted to map HD symptoms, assess the impact of symptoms on daily life, and explore the relevance of wearable sensors. Input from FDA will be incorporated into the study to ensure that it meets guidelines for endpoint development.

Results: We plan to begin enrollment in May 2025.

Conclusion: Digital measures of gait and chorea could serve as objective measures in HD clinical trials. MEND-HD aims to establish analytical validation and clinical meaningfulness of these measures, which will set the stage for use of digital measures of gait and chorea as treatment response endpoints in early HD.

References: 1. Helder DI, Kaptein AA, Van Kempen GM, Weinman J, Van Houwelingen JC, Roos RA. Living with Huntington’s disease: illness perceptions, coping mechanisms, and spouses’ quality of life. 2002;9(1):37-52.
2. Sherman CW, Iyer R, Abler V, Antonelli A, Carlozzi NE. Perceptions of the impact of chorea on health-related quality of life in Huntington disease (HD): A qualitative analysis of individuals across the HD spectrum, family members, and clinicians. Neuropsychol Rehabil. Published online March 2019:1-19. doi:10.1080/09602011.2018.1564675
3. Rao AK, Muratori L, Louis ED, Moskowitz CB, Marder KS. Spectrum of gait impairments in presymptomatic and symptomatic Huntington’s disease. Mov Disord. 2008;23(8):1100-1107.
4. Keren K, Busse M, Fritz N, Muratori L, Gazit E, Hillel I, Scheinowitz M, Gurevich T, Inbar N, Omer N, Hausdorff, Quinn L. Quantification of daily-living gait quantity and quality using.a wrist-worn accelerometer in Huntington’s Disease. Frontiers in Neurology. 2021; 12:719442. doi: 10.3389/fneuur.2021.719442.
5. Adams J, Waddell E, Chunga N, Quinn L. Digital measures in Huntington’s disease. In E. Thomas & G. Parkin (Eds). Biomarkers for Huntington’s disease. Improving Clinical Outcomes. Springer; Chalm, Switzerland. 2023.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/digital-measures-for-clinical-trial-endpoints-in-huntingtons-disease-mend-hd-study-design-and-status-update/