Huntington’s disease (HD) is a progressive neurodegenerative disorder that profoundly impacts individuals and their families. As new genetic and disease-modifying interventions emerge, the need for early and accurate assessment of disease progression has become crucial for successful therapeutic development. However, conventional clinical trial endpoints, such as the Unified Huntington’s Disease Rating Scale’s (UHDRS), Total Functional Capacity (TFC) and Total Motor Score (TMS), are often insufficiently sensitive to detect the subtle changes that occur in early HD. These clinic-based assessments provide only episodic snapshots of a patient’s condition and can be limited by subjective rating scales.
That’s where digital measures come in. Digital measures offer a promising solution by providing objective, sensitive, and quantitative assessments across a spectrum of impairments. These measures have the potential to better reflect real-life performance and detect subtle changes that traditional methods might miss. This article explores the potentially transformative role of digital measures in HD clinical trials, detailing what they are, why they are important, the types of measures being explored, and the challenges and future directions for their integration into research and care.
Digital Measures Defined
Digital measures refer to health-related information collected through technological devices. Devices like smartphones, smartwatches, or wearable sensors can help collect information about how we move, sleep, speak and think.
There are two main ways these devices gather information:
- Active monitoring: This means the wearer does a simple task, like tapping their fingers as part of an app assessment or taking a short walk while wearing a sensor, to help collect information.
- Passive monitoring: This happens in the background, without the wearer needing to do anything extra. For example, wearing a device on the wrist or waist that keeps track of daily steps, sleep quality, or balance while going about their day.
Because these devices can collect information all the time — not just during clinic visits — they give a fuller picture of how people with HD are functioning in everyday life.
Why Digital Measures are Important for Trial
Research in HD is focusing more on the earliest stages, even before there are obvious movement problems. To test new treatments and see if they are effective, researchers need tools that can identify slight shifts in health. Digital measures are important because:
- They’re more sensitive and objective: They can pick up on small variations in movement, thinking, or sleep that might be missed in a clinic appointment.
- They help with early decisions: By showing subtle changes over time, digital measures can help researchers figure out sooner if a treatment is working.
- They may become key research tools: In the future, information from these devices could become the main way to track progress in clinical trials, or at least an important back-up to more traditional tests.
Digital Measures Used in HD
Scientists are looking at many kinds of information to better understand HD, including:
- Movement: Measuring finger tapping, walking, balance, and involuntary movements (like chorea) with digital health technologies can reveal changes related to HD.
- Daily activity and sleep: Devices like Fitbits or actigraphy bands can keep track of movement and sleep, which may show early changes in HD.
- Cognition and speech: Simple tests and speech samples done through phone apps can detect changes in memory, attention or speech.
Some tools even combine several types of information into a single score, called a composite measure, giving a clearer sense of how HD is progressing.
How Digital Measures are Being Used
Recent research in HD is rapidly advancing digital measures across motor, cognitive, speech, sleep and activity domains. Composite indices like the Huntington’s Disease Digital Motor Progression Score (HDDMS), developed by Roche, integrate smartphone sensor data on balance, chorea, tapping and gait. Such measures have the potential to provide more sensitive clinical trial endpoints and reduce sample sizes required for robust conclusions.
Digital monitoring tools, including actigraphy and wearable devices, and app-based cognitive and speech assessments, are increasingly being incorporated into clinical trials, building on early motor assessments such as Q-motor and expanding to platforms like Roche’s HD Digital Monitoring Platform, which has gathered data from over 1000 HD participants. Studies such as KINECT-HD (Neurocrine) and others have incorporated wearable sensors to measure chorea and gait. This further validates the role of digital measures as sensitive secondary or exploratory endpoints and opens new avenues for efficient and meaningful monitoring in HD research and therapeutic development.
Measuring What Matters
It’s important that the information from digital devices reflects what matters most to people living with HD and their families. That’s why researchers are asking people with HD which symptoms worry them most, and whether the new digital measures track changes that they notice in day-to-day life. Understanding this connection will help make sure digital measures are valuable for everyone — not just scientists.
Challenges and What’s Next
There are still some hurdles to using digital measures widely:
- Proving they work: Many digital measures still need more research to show they can reliably track HD over time and in response to treatments.
- Standardizing collection protocols for measures of interest: With so many types of sensors and apps, researchers need to develop protocols that can be used across studies to allow for comparison of different interventions.
- Making them easy to use: Sometimes, using digital devices at home can be a hassle — like remembering to charge them or learning a new technology. Researchers are trying to make these tools as simple and helpful as possible.
- Getting approval: Agencies such as the FDA need strong proof before they can officially accept these digital measures in clinical trials. Some agencies are starting to support them as main measures in other diseases, which is a good sign for HD in the future.
A New Study Tests Efficacy
A new study called MEND-HD is testing how well digital measures work for people with early HD. Funded by the FDA, MEND-HD is completely remote. People wear special devices at home to track walking, movement, sleep, and more — and talk with researchers about which symptoms matter most to them. The anticipated outputs of MEND-HD include providing a roadmap for digital measures in clinical trials, defining the relationships between digital and traditional measures, and determining their sensitivity to track disease progression.
The study will also perform qualitative analysis of interviews and compare objective digital outcomes with patient-reported outcomes. The expected impact is to help establish these digital measures as treatment response endpoints in early HD. Furthermore, data from MEND-HD, including algorithms for gait and chorea, will be made available for researchers and clinicians.
Toward Better Tools and More Personalized Care
Digital measures have the potential to make life better for people with HD. By giving doctors and researchers more accurate, real-world information, these tools can make clinical trials more precise and may even reduce the need for frequent clinic visits. For this vision to become reality, more research is needed to prove these tools work and that they truly capture the experiences that matter to people living with HD.
With continued progress and collaboration, digital measures could help bring about a new era of personalized care and faster treatments for HD.