Neuromodulation Device Has Significant Effect on Essential Tremor Treatment

October 23, 2019

The director of the Parkinson’s Disease and Movement Disorders Center of Boca Raton and principal investigator of the PROSPECT study, offered insight into the clinical impact and advantages of the Cala Trio neuromodulation device.

Stuart Isaacson, MD

Recent data suggest that the use of a wrist-worn neuromodulation device can improve the symptoms and severity of essential tremor for patients. The device, the Cala Trio, was shown to be both safe and effective in topline data from the PROSPECT trial, significantly reducing symptoms and tremor power over a 3-month period.

The data show that at month 3, 62% of patients improved from severe/moderate to mild-slight on The Essential Tremor Rating Assessment Scale (TETRAS) scale, and 68% of patients improved from severe/moderate on the Bain & Findley Activities of Daily Living (ADLs) scale. By visit 3, TETRAS scores improved from 12.6 ±0.2 points at visit 1 to 9.8 ±0.2 points (P <.0001), while ADLs scores improved from 18.4 ±0.3 to 15.8 ±0.3 in the same time frame (P <.0001).1

To dive deeper into the findings and their clinical significance, NeurologyLive spoke with Stuart Isaacson, MD, director, Parkinson’s Disease and Movement Disorders Center of Boca Raton, and principal investigator of the study. Isaacson offered insight into the potential impact and advantages of the device as well as how it operates.

NeurologyLive: What should physicians take away from the PROSPECT trial data?

Stuart Isaacson, MD: Essential tremor is the most common movement disorder, and we've been plagued by medicines that lack consistent efficacy and often come with intolerable adverse effects. In the PROSPECT trial, using the Cala Trio device was able to demonstrate efficacy, especially efficacy around specific daily tasks with general tolerability. That's really the main take-home message.

Were there any particular data points that stood out?

There are 2 main data points that are compelling. One—because it's a device that was able to record both before and after over 21,000 therapy sessions—it really demonstrated that over 50% of patients experienced a 50% improvement in tremor power using analyses of the data that was captured.

But perhaps equally important, the device was worn at home by patients who were able to use it prior to performing daily tasks such as eating at mealtime or handwriting. And those patients were asked, when they came back in, to report their improvement using global impression scales, both completed by that patient and by the investigator clinician. These also demonstrated that 60% of patients noticed an improvement by wearing this device and having it stimulate for the session prior to doing the daily tasks.

How does the Cala Therapy device provide treatment for patients?

Remarkably, this device is worn on the wrist and has the ability to stimulate, in a somewhat similar manner to a TENS [transcutaneous electrical nerve stimulation] unit. It gives electrical stimulation over the median and radial nerves and it does this for approximately 40 minutes. This is titrated for each patient based on their tremor improvement, and this can be done in-home or in the clinic. Then the patient is able to wear this for 40 minutes, they take it off, and there's a subdued tremor because by stimulating peripheral nerves, it impacts the circuitry that involves the thalamus and cerebellum circuitry that underlies—we think—essential tremor generation patients. It's really peripheral nerve stimulation that can impact central circuitry.

What impact do you expect this to make in the tremor space?

This is the only device that has been studied in this manner with a primary end point that included the validated TETRAS scale, and the demonstration of moving patients from severe a moderate to mild or slight—probably about 60% of patients. We don't have that type of data with any available mechanical aid, pharmacological therapy. Only perhaps invasive surgical options, both deep brain stimulation and focused ultrasound may be able to improve tremor in this matter and to this degree.

Mechanical aids, where patients are asked to consider using heavier eating utensils, thicker and heavier writing instruments, special bowls and cups, and wearing wrist weights on the wrist, can sometimes dampen tremor. But the effect is usually transient with the rebounded and increase in tremor when they’re taken off. Pharmacological therapies really lack demonstrated efficacy—anecdotally, we can see improvements in some people, but we also have to be aware of systemic adverse effects. Many of these drugs can impair cognition, cause sleepiness, or other types of adverse effects that can limit patients’ ability to use some medications and titrate them high enough.

We’re really left in a therapeutic bind, where we don't have established mechanical or medical therapies and therapies that have been demonstrated to be useful before the Cala Trio had been surgical in nature. And I'm not aware that there are other devices like the Cala Trio that are being explored right now in large studies, nor are they available commercially.

What specific advantages does this offer, or challenges does this address, for patients and their physicians?

It allows patients to have an on-demand therapy that they can use prior to a daily task that, once calibrated according to their own tremor (which is done by the device), can lessen tremor so it will be lessened during the time they're using their hand to eat or right or whatever they're doing during that time period. In contrast, in trying to identify a medication, we tend to use beta-blockers like propranolol, anticonvulsants like primidone, benzodiazepines like clonazepam, and other medicines that are used off-label but have anecdotally been reported to, in some people, help tremor.

Often, though, most patients do not find significant tremor relief with these medications. They might find it with one or another, but not consistently, and they're often plagued by adverse effects from these medicines, which really limit their utility. Especially when we consider that essential tremor, while beginning in earlier life, tends to increase in severity, increase in the amplitude of the tremor, and impair daily tasks more and more as patients age into their 60s and 70s and even 80s or older. This is a vulnerable population if we're aiming to treat the tremor with drugs that cause sleeping or cognitive impairment, many patients choose, as time goes on, to not be treated for fear of causing those types of side effects.

Having availability of a device that is devoid of such systemic adverse effects really gives great empowerment to both clinicians who treat this disorder or have ignored the disorder for lack of good treatment options for the patients, and especially for patients to be able to have something that they can wear for 40 minutes and then have less tremor for some time afterwards. And they can wear it a couple of times a day. It really changes the treatment paradigm.

What do you feel will be the ultimate impact of this device?

The idea that we can use a noninvasive neuromodulation therapy and demonstrate efficacy using validated scales like TETRAS, and global impression scales from the patient and the investigator—and have a large volume of data that are collected before and after the treatment sessions from this device—really gives strong weight to the idea that we may now be able to treat patients who before were left untreated, or were treated and had intolerability with the pharmacological agents.

I think it's an important advancement in the movement disorder world and because essential tremor is so common—like 10 times or more common than Parkinson disease—these are patients who are really seen by general neurologists. It'll be important to try to get this information out not only to people who see a lot of movement disorders but to general neurologists, and indeed, primary care doctors who are seeing a lot of these patients who may have been evaluated over the years and told there are no good treatment options or tried 1 or 2 of the medications had adverse effects and stopped them. We need to try to reach out to patients and their clinicians to let them know that there's another option, and one that may improve tremor without the systemic adverse effects.

Transcript edited for clarity.

REFERENCE

Isaacson S, Peckham E, Waln O, et al. Non-Invasive, At-Home Use Neuromodulation Device Provides Symptomatic Relief from Essential Tremor: Results From The PROSPECT* Study. Presented at: International Congress of Parkinson’s Disease and Movement Disorders; September 22 to 26, 2019; Nice, France. cdn.filestackcontent.com/UK0rDf9lQXeqS8cUiBif. Accessed October 20, 2019.