Comparing schedules for a brain stimulation treatment

The goal of this clinical trial is to compare the efficacy and safety of different Intervention Intervals of subthalamic nucleus-targeted transcranial temporal interference stimulation (STN-tTIS) in patients with Parkinson disease. Previous studies suggest that STN-tTIS may improve motor symptoms in people with Parkinson disease. However, most previous studies evaluated only one stimulation session. It remains unclear how often STN-tTIS should be administered during a repeated treatment course and whether shorter intervention intervals stimulation produces greater or longer-lasting improvement without increasing adverse events. The main questions this study aims to answer are: 1. Does STN-tTIS administered five times weekly improve motor symptoms more than standard medication treatment alone at the end of the 2-week treatment period? 2. Do once-weekly, twice-weekly, and five-times-weekly STN-tTIS produce different changes in motor symptoms? 3. Does the STN-tTIS intervention intervals influence how long its effects persist after treatment? 4. Do the different intervention intervals have different effects on non-motor symptoms, quality of life, cognitive function, and safety? Participants will be randomly assigned to receive STN-tTIS once weekly, twice weekly, or five times weekly for 2 weeks, or to continue standard antiparkinsonian medication without additional stimulation. All participants will maintain a stable medication regimen during the study. Their motor and non-motor symptoms will be assessed during the treatment period and during a subsequent 2-week follow-up period.

Parkinson disease (PD) is a progressive neurodegenerative disorder characterized by both motor and non-motor symptoms that substantially impair quality of life. Although pharmacological therapy remains the standard treatment, long-term medication use is frequently associated with motor fluctuations and treatment-related complications. Transcranial temporal interference stimulation (tTIS) is a novel noninvasive neuromodulation technique capable of selectively modulating deep brain structures without surgery. Previous pilot studies have demonstrated that subthalamic nucleus-targeted tTIS (STN-tTIS) may improve motor symptoms in patients with PD. However, existing studies have primarily evaluated the immediate effects of single-session stimulation, and the optimal intervention interval for repeated STN-tTIS has not yet been established. The objective of this multicenter clinical trial is to evaluate whether different intervention intervals, defined as once-weekly, twice-weekly, and five-times-weekly STN-tTIS administration, result in different therapeutic effects in patients with PD and to compare their efficacy and safety. The study will also investigate whether the intervention interval influences the durability of clinical improvement following completion of the intervention. Approximately 60 participants with PD will be enrolled and randomly assigned to one of three active STN-tTIS treatment groups with different intervention intervals or to a control group receiving standard medical therapy alone. All participants will continue a stable antiparkinsonian medication regimen throughout the study. The treatment period will last 2 weeks, followed by a 2-week follow-up period. Clinical efficacy will be evaluated primarily by changes in motor symptoms, while additional assessments will evaluate non-motor symptoms, sleep, quality of life, cognitive function, and safety. This study will provide information regarding the influence of intervention intervals on the efficacy and safety of repeated STN-tTIS in patients with Parkinson disease and may help inform future treatment strategies.