Smartphone-based tests may better detect Huntington’s progression
Study indicates incorporating measure in trials could have multiple benefits
The Huntington’s Disease Digital Motor Score (HDDMS), a new measure based on four motor tests that are done through a smartphone app, may be able to detect Huntington’s disease progression with greater sensitivity than current standard tools, a study reports.
“Our findings suggest that incorporating the HDDMS in clinical trials will help to give clearer answers about whether a potential treatment is working, with fewer participants or shorter lead times than conventional measures,” Ed Wild, PhD, a senior author of the study at University College London (UCL) and the associate director of UCL’s Huntington’s Disease Center, said in a university news story. “What’s more, the fact that the HDDMS is evaluated in a five-minute assessment in people’s homes makes it convenient and potentially more meaningful than in-clinic measures of motor impairment.”
The study, “A digital motor score for sensitive detection of progression in Huntington’s disease,” was published in Brain.
Differences seen between HDDMS and standard method of measure
Huntington’s is a genetic disorder that causes problems with motor and cognitive function that tend to get worse over time. A standard way to measure Huntington’s progression is to use the composite Unified Huntington’s Disease Rating Scale (cUHDRS), a tool that incorporates several standardized tests of movement, cognitive function, behavior, and functional independence.
Although the cUHDRS can be an effective way to measure Huntington’s progression, it is not a particularly sensitive tool, with scores only changing when a patient is experiencing a fairly substantial change in their functional abilities, according to the researchers.
This means clinical trials using the cUHDRS to assess how investigational treatments affect Huntington’s progression tend to need many participants and take a long time to get meaningful results.
“More sensitive tools to measure disease progression are particularly valuable in rare diseases like Huntington’s disease,” Wild said. “The fewer people there are who can possibly participate in clinical trials, the more important it becomes to minimise trial burden and size.”
In this study, researchers at UCL and biotech company Roche worked with people with Huntington’s to create a smartphone-based measure of Huntington’s progression.
The HDDMS is a composite measure that includes four simple motor tasks to assess chorea — a hallmark Huntington’s symptom characterized by involuntary movements — of the trunk and upper limbs, fine motor skills in the fingers, and lower limb motor function.
The tasks involve asking patients to do things such as tapping on their screen in a set pattern or walking a short distance. They can be done quickly and at home, without any equipment other than a smartphone.
Measure more sensitive to small changes in Huntington’s progression over time
The researchers tested and validated the HDDMS using data from more than 1,000 people with Huntington’s, as well as several dozen people without the disease used for comparison. They were enrolled across four observational studies or interventional clinical trials.
Most of the Huntington’s patients had participated in the Phase 3 GENERATION HD1 clinical trial (NCT03761849), which tested Roche’s experimental treatment tominersen in more than 700 people with established Huntington’s. Dosing was stopped early due to negative results.
Data from GENERATION HD1 indicated HDDMS scores correlated closely with scores on the cUHDRS — in other words, the smartphone-based score generally lined up well with the established metric.
By using the HDDMS, changes in motor progression can be identified with a significantly reduced sample size.
More importantly, the HDDMS was found to be more sensitive to small changes over time. HDDMS was even sensitive among patients with stage 2 or early intermediate Huntington’s, who tend to show fairly subtle changes over time.
Because the HDDMS could detect smaller changes indicative of disease progression relative to the standard cUHDRS, the researchers estimated using the new tool in clinical trials can reduce, by up to 80%, the number of participants needed to detect a substantial, and significant, difference in disease progression.
“By using the HDDMS, changes in motor progression can be identified with a significantly reduced sample size,” which can also “lead to reduced study duration due to faster recruitment,” the researchers wrote. “This is particularly useful for a rare neurodegenerative disease such as [Huntington’s], where progression occurs slowly, clinical manifestations can be highly variable and recruiting sufficiently large study [groups] for early-stage trials may be challenging.”
Given that the study was limited to people participating in four select studies that didn’t include those with very early or late-stage Huntington’s, further work is needed to validate the HDDMS, the scientists noted. More work also will be needed to see how well the HDDMS can track disease evolution over years of follow-up.
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