In Essential Tremor, Transcutaneous Peripheral Nerve Stimulation was Associated with Functional Improvements

For adults with essential tremor (ET), artificial intelligence (AI)-driven transcutaneous peripheral nerve stimulation (TPNS) therapy was associated with significant improvements in functional outcomes compared with sham therapy. The findings of the prospective, randomized, multicenter TRANQUIL clinical trial (NCT06235190), which were published in JAMA Neurology, suggest that continuous peripheral nerve stimulation could offer a noninvasive treatment alternative for people with ET who are not candidates for, or wish to avoid, surgical interventions.

The TRANQUIL trial enrolled 125 participants across 12 neurology centers in the United States and China. Participants were randomized 2:1 to receive either active (n=83) or sham (n=42) TPNS therapy for 90 days. The wearable TPNS device, worn on the wrist, continuously modulated stimulation to the radial, median, and ulnar nerves based on real-time movement data via cloud-based AI algorithms. The primary end point of the study was change in score on the modified Activities of Daily Living (mADL) subscale of the Essential Tremor Rating Assessment Scale (TETRAS). The study analysis at 90 days included 62 participants in the active stimulation group and 36 individuals in the sham stimulation group.

Key results at 90 days included the following:

• For participants in the active TPNS group, mADL scores were reduced by a mean of 6.9 points (95% CI, 5.4 to 8.4) vs 2.7 points (95% CI, 1.3 to 4.0) in the sham group.
• Clinically meaningful improvement (≥20% reduction in mADL) was achieved by 61.3% of active TPNS recipients (n=38 of 62) vs 25.0% of sham treatment recipients (n=9 of 36).
• Participant- and clinician-reported global improvement scores significantly favored active TPNS treatment.
• Mild skin irritation was the most common adverse event, occurring in 28.9% of active TPNS users; no serious adverse events were reported.

Source: Ondo WG, Lv W, Zhu X, et al. Transcutaneous Peripheral Nerve Stimulation for Essential Tremor: A Randomized Clinical Trial. JAMA Neurol. Published online October 20, 2025. doi:10.1001/jamaneurol.2025.3905