Transcutaneous Peripheral Nerve Stimulation for Essential Tremor: A Randomized Clinical Trial.

Abstract

Essential tremor (ET) is the most common form of arm tremor. Transcutaneous peripheral nerve stimulation (TPNS) can modulate the central tremor-generating network. To investigate whether an artificial intelligence (AI)-driven TPNS device is superior to a sham device in reducing ET. A randomized clinical trial was conducted from February 7 through August 9, 2024, in 12 outpatient neurology clinics in the United States and China. Participants were adults with upper-extremity tremor and a clinical diagnosis of ET, a tremor severity score of 2 or higher on 1 of the Essential Tremor Rating Assessment Scale (TETRAS) performance subscale tasks, a total performance subscale score of at least 7, and familiarity with operating a smartphone and connecting to Wi-Fi at home. They were randomized 2:1 to receive active TPNS or sham stimulation, stratified by use of ET medications and tremor severity. After the devices were fitted, the participants were instructed to use them during waking hours for 90 days. A wearable neuromodulation device that stimulates the radial, median, and ulnar nerves and uses AI to continuously adjust stimulation settings in real time. The primary outcome was change in daily activities as measured by the modified Activities of Daily Living (mADL) subscale of TETRAS at 90 days in the intention-to-treat population. Of 133 screened, 125 were randomized to receive TPNS (n = 83) or sham (n = 42) treatment. The mean (SD) age was 64.9 (13.1) years, 62 (49.6%) were female and 63 (50.4%) male, and the mean (SD) tremor duration was 11.4 (13.1) years. At 90 days, the mADL score was reduced by 6.9 points (95% CI, 5.4-8.4) in the TPNS group vs 2.7 points (95% CI, 1.3-4.0) in the sham group (P < .001). Skin irritation, the most common device-related adverse event, occurred in 28 of 83 participants (33.7%) in the TPNS group and 2 of 42 (4.8%) in the sham group. Nausea, arthralgia, worsening of existing arthritis in the thumb, muscular weakness, and involuntary muscle contractions each occurred in 1 participant, all in the TPNS group. The TPNS device improved activities related to upper limb tremor at 90 days and could be an effective noninvasive ET treatment. ClinicalTrials.gov Identifier: NCT06235190.