This clinical trial will evaluate the efficacy of accelerated Temporal Interference Stimulation (TIS) as a therapeutic intervention for individuals diagnosed with Parkinson's disease. Different frequency TIS will be delivered targeting the bilateral subthalamic nuclei of the brain according to the patient's clinical symptoms. Specifically, the basal thalamic nuclei on the side opposite to the side where the patient's symptoms are most severe receive stimulation at 130 Hz, whilst those on the other side receive stimulation at 60 Hz. The primary objective is to assess whether accelerated TIS yields measurable improvements in motor performance and verbal speech function among enrolled subjects. Functional magnetic resonance imaging (fMRI) will be adopted as an auxiliary imaging modality to objectively characterize underlying cerebral functional alterations induced by accelerated TIS intervention. The core scientific research questions to be addressed in this trial are listed as follows:
Will different frequency accelerated TIS administered to the bilateral subthalamic nuclei produce significant improvements in motor function and cognitive function among enrolled subjects with Parkinson-related disorders? What quantitative and qualitative modifications in cerebral functional activity will be detected via fMRI after standardized accelerated TIS intervention administration? Investigators will implement a two-arm parallel controlled comparative design for all enrolled eligible subjects. This design remains a parallel design, with two independent groups of subjects receiving different active interventions simultaneously rather than a sham control. All confirmed Parkinson's disease patients will undergo standardized random grouping and be allocated into two independent research arms. Subjects in the experimental arm will receive continuous, standardized TIS intervention targeting bilateral subthalamic nuclei, with the basal thalamic nuclei on the side opposite to the side where the patient's symptoms are most severe receiving stimulation at 130 Hz, and those on the other side receiving stimulation at 60 Hz. Subjects in the control arm will receive continuous, standardized TIS intervention targeting bilateral subthalamic nuclei with bilateral 130 Hz stimulation. The control intervention adopts identical operation procedures, equipment wearing mode and on-site operating environment as the formal TIS intervention, with the only difference being the stimulation frequency setting (bilateral 130 Hz in the control arm versus asymmetric frequency in the experimental arm). Rigorous controlled grouping design will ensure objective, verifiable data support for verifying the actual intervention efficacy of different frequency TIS modes on motor dysfunction and speech impairment in Parkinson-related patients, and will also help to clarify the potential advantages of asymmetric frequency TIS over bilateral same-frequency TIS.
All enrolled subjects will complete the following standardized trial procedures in full compliance with the trial protocol:
Receive continuous targeted intervention of either formal asymmetric frequency TIS (130 Hz on the contralateral side of severe symptoms, 60 Hz on the ipsilateral side) or bilateral 130 Hz TIS control intervention on bilateral subthalamic nuclei, with consecutive 5-day fixed-course administration in strict accordance with trial operating specifications.
Complete unified fMRI brain scanning examinations and standardized motor function as well as speech function quantitative evaluation assessments at two fixed time nodes, including the baseline time point before intervention initiation and the follow-up time point after all intervention courses are completed.
Truthfully record all adverse reactions and abnormal physical discomfort symptoms that occur throughout the whole intervention and follow-up observation cycle in standardized adverse event registration forms.
Idiopathic Parkinson's disease diagnosed by neurologists according to the Movement Disorder Society Clinical Diagnostic Criteria;
Hoehn and Yahr stage 1.5-3.0;
Stable levodopa-based antiparkinsonian medication for at least 4 weeks before enrolment, with no planned medication change during the trial period;
Ability to walk independently;
Any contraindication to MRI or tTIS, including claustrophobia or ferromagnetic intracranial or subcutaneous implants;
Significant systemic disease that could increase study risk or interfere with trial participation;
Neurological disorders other than Parkinson's disease;
Major psychiatric disorder or severe depression or anxiety;
Parallel
Temporal Interference Stimulation
DeviceSequential bilateral subthalamic nucleus (STN) temporal interference electrical stimulation, administered twice daily (40 minutes per session, ≥1 hour rest interval between sessions). Stimulation targets are bilateral STN, with individualized electrode placement and current intensity determined via personalized modeling from patient MRI data. A fixed carrier frequency of 2000 Hz is used for all STN stimulation. Specifically, therapeutic temporal interference stimulation with an envelope frequency of 130 Hz is delivered to the STN contralateral to the patient's most symptomatic side, while stimulation with an envelope frequency of 60 Hz is applied to the STN ipsilateral to the most symptomatic side to produce targeted therapeutic interference fields.
Temporal Interference Stimulation
DeviceSequential bilateral subthalamic nucleus (STN) temporal interference electrical stimulation (active control), administered twice daily (40 minutes per session, ≥1 hour rest interval between sessions). Stimulation targets are bilateral STN, with individualized electrode placement and current intensity determined via personalized modeling from patient MRI data. The active control stimulation uses two distinct high frequencies (2000 Hz and 2130 Hz) to generate a therapeutic interference field.
The score of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS-III)
The MDS-UPDRS-III is a standardized assessment tool to evaluate motor function symptoms in people with Parkinson's disease.It has a scoring range of 0 to 132 points, with higher scores meaning more severe motor disorders.
The scores of Mini-BESTest
The Mini-BESTest is a clinical assessment tool for evaluating balance function. It assesses the balance control system across multiple domains, with a scoring range of 0 to 28 points; higher scores indicate better balance function.
10-Meter Walk Test
The 10-Meter Walk Test assesses gait speed and functional mobility by measuring the time required to walk 10 meters. Increased time reflects slower walking and worse mobility.
Voice intensity
Voice intensity is measured using Praat software. Voice intensity, expressed in dB SPL, reflects the loudness of the voice. This indicators is used to objectively evaluate the functional status of the subjects' vocal system. Abnormalities in voice intensity may indicate impairments in vocal cord movement, laryngeal muscle control, or related neural regulation, which is of great significance for assessing the severity of vocal function disorders and the effect of intervention.
Velocity of center of pressure (COP) sway
Center of pressure (COP) sway velocity of subjects on stable and unstable surfaces is measured via a balance board during two standing conditions: single-task quiet standing and dual-task standing. The dual-task standing requires subjects to continuously perform serial subtraction of 7 from random numbers ranging from 400 to 600 while maintaining standing posture. The balance board records COP movement speed under both single-task and dual-task standing states. This indicator objectively assesses balance control and adaptability to different surfaces; abnormal increases indicate impaired balance, aiding evaluation of balance disorder severity and intervention effectiveness.
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Ke Dong, MD
Lead sponsor
First Affiliated Hospital, Sun Yat-Sen University
Sponsor institution
