Measuring Digital Clinical Endpoints in Huntington's Disease (MEND-HD)

PROJECT SUMMARY (ABSTRACT)
As genetic and disease-modifying interventions emerge, there is an urgent need for early and accurate
assessment of disease-specific motor impairments in people with Huntington’s disease (HD). Traditional
measures are subjective and episodic and have a limited ability to capture early, subtle motor features. Digital
measures have the potential to remotely quantify disease-specific impairments in individuals with HD. A key
next step is to evaluate the most promising digital measures in the early stages of HD.
Gait impairments and involuntary choreic movements are clinical hallmarks of HD and two of the earliest motor
signs. Chorea, which is characterized by involuntary writhing movements, can affect gait characteristics and
make conventional approaches to quantifying gait using wearable sensors inaccurate in HD. Our pilot work has
shown that wearable sensors can evaluate the quantity and quality of daily living gait in people with HD, even in
the presence of chorea, with the aid of tailored machine learning. Exciting initial findings also suggest that chorea
severity can be captured using digital health technologies (DHTs) like wearable sensors. Daily physical activity,
heart rate variability, and sleep also differ in individuals with HD and healthy controls. All of these measures have
the potential to be meaningful endpoints in HD clinical trials, but critical gaps first need to be addressed.
We aim to demonstrate the reliability, validity, and meaningfulness of two key digital measures, daily living
mobility (gait) and chorea, captured remotely and continuously using wearable sensors. We will also explore
daily physical activity, heart rate variability, and sleep. In this remote, cross-sectional study, 40 individuals with
early HD (HD Integrated Staging System, HD-ISS Stage 2, and early Stage 3) and 20 control participants will
wear two sensors (trunk and wrist) for 1 and 2 weeks, respectively, and will complete telehealth assessments
and interviews. Our long-term objective is to fully establish these digital measures as drug development tools
and treatment response endpoints in early HD. Our two specific aims are: 1) demonstrate the construct validity
and test-retest reliability of a) real-world gait and chorea and b) daily living physical activity, heart rate
variability, and sleep quality using wrist-worn wearable sensors in people with early-stage HD; and 2) a) to map
personally bothersome and important symptoms/impacts of HD and assess relevance of selected digital
measures and b) to evaluate the relationship between the digital measures and patient-reported outcomes.
The proposed work will be the first time that our innovative symptom mapping approach is applied to HD,
the first time that DHTs are connected to patient-reported meaningfulness in HD, and the first time that real-
world study of gait and chorea in HD is assessed as a function of the recently developed HD-ISS staging. This
will also be the first study that brings together recently developed HD functional scales, patient symptom
mapping, and novel digital measures. The study will inform larger-scale validation efforts and clinical endpoint
studies in HD and other, more common diseases with involuntary movements (e.g. Parkinson’s disease).

Grant Number: 5U01FD008429-02
NIH Institute/Center: FDA
Principal Investigator: Jamie Adams