The StepWatch Activity Monitor, unlike the 6-minute walk test, was able to detect progressive deterioration in patients with Charcot-Marie-Tooth disease (CMT) over the course of one year and may be a suitable measure of outcomes in clinical studies of potential treatments, a study reports.
The study, “Are novel outcome measures for Charcot-Marie-Tooth disease sensitive to change? The 6-minute walk test and StepWatchTM Activity Monitor in a 12-month longitudinal study,” was published in Neuromuscular Disorders.
CMT is the most common heritable disease that affects the peripheral nervous system — the network of nerves responsible for controlling movement and sensation in the limbs.
Previous clinical trials assessing the efficacy of ascorbic acid (vitamin C) and Pharnext‘s PTX3003 (a combination of baclofen, naltrexone, and sorbitol) in treating CMT failed to provide significant results, possibly due to differences regarding optimal outcome measures for such studies, the researchers note.
A previous study by the same research team in Italy showed the 6-minute walk test (6MWT) and the StepWatch Activity Monitor (SAM) were both suitable measures to evaluate disease progression in a large group of CMT patients.
In this study, the team’s goal was to evaluate whether these two measures are able to detect clinical changes occurring over the course of one year in a group of CMT patients.
Initially, the longitudinal, prospective, multi-center study enrolled 169 CMT patients. From these, 149 people — 89 with CMT1A, 25 with CMT1B and 35 with X-linked CMT — were re-evaluated one year later using the 6MWT, SAM and other conventional measures of CMT. These were the CMT- Neuropathy Score second version (CMTNSv2), the maximal voluntary isometric contraction (MVIC) to assess muscle strength, the 10-meter walking test, and the 36 item Short Form questionnaire (SF-36) that assesses patients’ quality of life.
According to guidelines defined by the American Thoracic Society (ATS), the 6MWT measures the distance a patient is able to cover in six minutes while walking on a flat and rigid surface. SAM measures the frequency, duration, and intensity of muscle activity during daily life activities using a lightweight device placed on the patients’ ankle and worn throughout the day.
With SAM, measures using CMTNSv2 and MVIC detected a significant worsening of patients’ symptoms at 12 months after the beginning of the study — an “objective worsening independent of physician and patient impression,” the researchers wrote.
“In conditions like CMT, where disease progression is very slow, it is essential to adopt OMs [outcome measures] that are highly sensitive to small changes,” the team wrote. “The results of the current study confirm that CMT patients worsen over a 12-month period, as demonstrated by change in the CMTNSv2 and MVIC of upper and lower limbs.”
In contrast, the 10-meter walking test, patients’ quality of life as measured by the SF-36, and the 6MWT captured no changes in disease progression in these patients over the year analyzed.
“SAM is inexpensive (about 400 euros) is probably affordable for most clinical trials conducted on rare diseases. Importantly, a sample size of 56 subjects is sufficient to reach results in future trials. This number, quite low, is essential for use in a rare disease trial,” the study noted.
“The current study confirmed clinical worsening of CMT over 12 months detected by the CMTNSv2, SAM and myometry measures. In spite of this worsening the QoL [quality of life] remained stable, probably because of compensatory strategies. SAM, a novel OM, was sensitive for detecting worsening in the natural course of CMT, but now requires testing in a clinical therapeutic trial,” the researchers concluded.