This large randomized, double-blind, multicenter trial will test whether precision neuroimaging-guided continuous theta-burst stimulation targeting the left supplementary motor area improves motor symptoms in 290 Parkinson's patients versus sham, with primary outcome MDS-UPDRS III at day 8 and…

A positive result would provide high-quality clinical evidence for a noninvasive, reproducible neuromodulation therapy as an adjunctive symptomatic treatment for PD motor deficits and support broader translational development of precision rTMS protocols.

BACKGROUND: As an innovative noninvasive neuromodulation technology, repetitive transcranial magnetic stimulation (rTMS) has demonstrated efficacy in improving motor symptoms in patients with Parkinson's disease (PD). The supplementary motor area (SMA) has been identified as a brain region significantly associated with motor symptoms in PD patients. However, no large-sample clinical studies have yet established the clinical efficacy of rTMS, guided by neuroimaging navigation, targeting the SMA in patients with PD. METHODS: This study describes a randomized, double-blind, placebo-controlled, multicenter study designed to recruit 290 patients with primary PD. Participants will be randomly assigned to receive either real stimulation or sham stimulation, with the left SMA undergoing 7 days of continuous theta-burst stimulation (cTBS). The primary outcome measure is the changes in MDS-UPDRS III scores assessed from baseline to the end of 7-day treatment (on day 8). The secondary outcome is changes in other clinical symptom scores from baseline to day 8 and weeks 5 and 9. The study is expected to be conducted across eight medical centers in China, commencing in 2024 and concluding in 2026. DISCUSSION: This study will evaluate the clinical efficacy and safety of cTBS targeting the left SMA in patients with PD. These findings may offer a new therapeutic approach for PD. TRIAL REGISTRATION: ClinicalTrials.gov NCT06383247 (registered April 2024).