Non-Invasive Transcutaneous Afferent Patterned Stimulation Therapy Offers Action Tremor Relief in Parkinson's Disease

Salima Brillman; Pravin Khemani; Stuart H Isaacson; Rajesh Pahwa; Ruta Deshpande; Vivien Zraick; Apoorva Rajagopal; Dhira Khosla; Kathryn H Rosenbluth

doi:10.5334/tohm.762

Non-Invasive Transcutaneous Afferent Patterned Stimulation Therapy Offers Action Tremor Relief in Parkinson's Disease

Tremor Other Hyperkinet Mov (N Y). 2023 Aug 23:13:25. doi: 10.5334/tohm.762. eCollection 2023.

Authors

Salima Brillman¹, Pravin Khemani², Stuart H Isaacson³, Rajesh Pahwa⁴, Ruta Deshpande⁵, Vivien Zraick⁵, Apoorva Rajagopal⁵, Dhira Khosla⁵, Kathryn H Rosenbluth⁵

Affiliations

¹ Parkinson's Disease and Movement Disorders Center of Silicon Valley, Palo Alto, CA, US.
² Swedish Neuroscience Institute, Seattle, WA, US.
³ Parkinson's Disease and Movement Disorders of Boca Raton, Boca Raton, FL, US.
⁴ University of Kansas Medical Center, Kansas City, KS, US.
⁵ Cala Health, Inc., San Mateo, CA, US.

Abstract

Background: Many patients with Parkinson's disease (PD) experience action tremor (including postural and kinetic tremors) that impair activities of daily living. Transcutaneous afferent patterned stimulation (TAPS) is a non-invasive neuromodulation therapy that modulates tremorgenic activity at the ventral intermediate nucleus (VIM). Most TAPS evidence evaluated relief of action tremor associated with essential tremor (ET). This study evaluated whether TAPS results in similar relief of action tremor associated with PD.

Methods: Forty PD patients with action tremors were enrolled in a prospective, single-arm, open-label study with four weeks of unsupervised at-home TAPS sessions in the dominant hand twice daily in between supervised TAPS sessions at two telemedicine appointments. The primary endpoint was change in tremor power as measured by the on-board accelerometer before and immediately after a stimulation session. Additional study endpoints included change in Movement Disorder Society-Sponsored Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS), change in Bain and Findley Activities of Daily Living (BF-ADL) scale, and clinician and patient global impressions of improvement (CGI-I and PGI-I).

Results: TAPS reduced tremor power by 64% (54%-79%) (median (interquartile range), p < 0.001), with 79% of patients experiencing at least 50% reduction. When comparing pre-stimulation scores at visit 1 to post-stimulation scores at visit 2, TAPS improved per-task MDS-UPDRS III ratings of postural and kinetic tremors (0.6 ± 0.5, t(34) = 7.05, p < 0.001) and per-task patient-ratings of BF-ADL ADL upper limb motion ratings (0.5 ± 0.5, t(34) = 5.69, p < 0.001). Clinicians reported improvement in 78-83% of patients and 75-80% of patients reported improvement. Adverse events, most commonly skin reaction at the stimulation site, occurred in 18% of patients.

Conclusion: Objective, clinician-rated, and patient-rated assessments demonstrated that TAPS provided clinically meaningful relief of action tremor in patients with PD.

Trial registration: ClinicalTrials.gov NCT05540626.

Keywords: Action Tremor; Neuromodulation; Non-invasive; Parkinson’s Disease; Transcutaneous Afferent Patterned Stimulation.

Publication types

Clinical Trial
Research Support, Non-U.S. Gov't

MeSH terms

Activities of Daily Living
Essential Tremor* / therapy
Humans
Parkinson Disease* / complications
Parkinson Disease* / therapy
Prospective Studies
Tremor

Associated data

ClinicalTrials.gov/NCT05540626

Grants and funding

This study was sponsored by Cala Health, Inc.