Prospective Home-use Study on Non-invasive Neuromodulation Therapy for Essential Tremor

Abstract

Highlights This prospective study is one of the largest clinical trials in essential tremor to date. Study findings suggest that individualized non-invasive neuromodulation therapy used repeatedly at home over three months results in safe and effective hand tremor reduction and improves quality of life for many essential tremor patients. Background: Two previous randomized, controlled, single-session trials demonstrated efficacy of non-invasive neuromodulation therapy targeting the median and radial nerves for reducing hand tremor. This current study evaluated efficacy and safety of the therapy over three months of repeated home use. Methods: This was a prospective, open-label, post-clearance, single-arm study with 263 patients enrolled across 26 sites. Patients were instructed to use the therapy twice daily for three months. Pre-specified co-primary endpoints were improvements on clinician-rated Tremor Research Group Essential Tremor Rating Assessment Scale (TETRAS) and patient-rated Bain & Findley Activities of Daily Living (BF-ADL) dominant hand scores. Other endpoints included improvement in the tremor power detected by an accelerometer on the therapeutic device, Clinical and Patient Global Impression scores (CGI-I, PGI-I), and Quality of Life in Essential Tremor (QUEST) survey. Results: 205 patients completed the study. The co-primary endpoints were met (p≪0.0001), with 62% (TET-RAS) and 68% (BF-ADL) of 'severe' or 'moderate' patients improving to 'mild' or 'slight'. Clinicians (CGI-I) reported improvement in 68% of patients, 60% (PGI-I) of patients reported improvement, and QUEST improved (p = 0.0019). Wrist-worn accelerometer recordings before and after 21,806 therapy sessions showed that 92% of patients improved, and 54% of patients experienced ≥50% improvement in tremor power. Device-related adverse events (e.g., wrist discomfort, skin irritation, pain) occurred in 18% of patients. No device-related serious adverse events were reported. Discussion: This study suggests that non-invasive neuromodulation therapy used repeatedly at home over three months results in safe and effective hand tremor reduction in many essential tremor patients.

Transcutaneous Afferent Patterned Stimulation Therapy Reduces Hand Tremor for One Hour in Essential Tremor Patients

“…Similarly, the magnitude of acute (i.e., immediately poststimulation) tremor improvement reported in this study is consistent with the acute tremor improvements observed in previous TAPS studies. This study found an average FTM-CRS improvement of 0.6 points immediately after stimulation (Figure 2), which was comparable to improvements reported in other studies using similar clinical rating scales [0.3-0.8 point improvement in various upper limb tasks in the Tremor Research Group Essential Tremor Rating Assessment Scale (Elble, 2016), and 0.3-1 point improvement in the Bain & Findley Activities of Daily Living scale (Bain et al, 1993;Pahwa et al, 2019;Isaacson et al, 2020)]. The median 3.2-fold improvement (70% reduction) in postural hold tremor power immediately after the end of stimulation ( Figure 3A) in this study is comparable to the range of postural hold tremor power improvements reported in a 3 month at-home clinical trial (Isaacson et al, 2020).…”

“…reduce or discontinue use of medications due to the side effects present at the doses required to sufficiently treat tremor (Koller and Vetere-Overfield, 1989;O'Suilleabhain and Dewey, 2002;Zesiewicz et al, 2005;Pal, 2011;Hedera et al, 2013). While TAPS has been shown here and in other studies to have a much lower adverse event rate than medications (Lin et al, 2018;Pahwa et al, 2019;Isaacson et al, 2020), this single-session study alone is insufficient to conclude whether 60 min of benefit after 40 min of stimulation is sufficient for some patients to adopt TAPS therapy into their tremor treatment routine. Future work to examine patient satisfaction with receiving 60 min of benefit after each therapy session, the time course of repeated TAPS throughout the day (i.e., mimicking medication usage), and how TAPS therapy interacts with medication usage would provide valuable guidance for physicians prescribing only TAPS, only medications, or TAPS and medication combined.…”

“…The post-stimulation duration of benefit objectively measured in this study is comparable to patients' self-reported durations of benefit in other studies. In a recent 3-month clinical trial that tracked 205 patients using TAPS therapy twice daily at home, 64% of patients reported their tremor relief persisted beyond the end of stimulation (Isaacson et al, 2020). For these patients reporting extended relief, the median self-reported poststimulation duration of benefit was 60 min (Isaacson et al, 2020).…”

“…A stimulation session consisted of 40 min of continuous stimulation at the chosen amplitude. This stimulation protocol was consistent with protocols used in previous studies evaluating acute efficacy of TAPS (Lin et al, 2018;Pahwa et al, 2019;Isaacson et al, 2020). Safety was assessed by analyzing the reported adverse events.…”

“…TAPS consists of bursts of non-invasive electrical stimulation applied to the median and radial nerves that alternate at the frequency of a patient's tremor. Two randomized, shamcontrolled clinical trials (Lin et al, 2018;Pahwa et al, 2019) and one 3-month at-home clinical trial (Isaacson et al, 2020) have shown that 40 min of TAPS therapy reduces tremor severity and improves patients' abilities to complete daily living tasks. However, these trials assessed tremor immediately after the end of stimulation, consistent with the clinical observation that traditional DBS quickly loses efficacy once stimulation is turned off (Lopiano et al, 2003;Temperli et al, 2003;Perera et al, 2015).…”