Different Frequency Temporal Interference Stimulation on Bilateral Subthalamic Nucleus for Parkinson's Disease

A Single-Center, Double-Blind Randomized Controlled Trial of Different Frequency Temporal Interference Stimulation Applied to Bilateral Subthalamic Nucleus for Improving Motor and Vocal Functions in Patients With Parkinson's Disease.

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 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. 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. Subjects in the control arm will receive matched sham stimulation intervention. Sham stimulation adopts identical operation procedures, equipment wearing mode and on-site operating environment as formal TIS, with no valid neuromodulation therapeutic effect generated. Rigorous controlled grouping design will ensure objective, verifiable data support for verifying the actual intervention efficacy of different frequency TIS on motor dysfunction and speech impairment in Parkinson-related patients.

All enrolled subjects will complete the following standardized trial procedures in full compliance with the trial protocol:

Receive continuous targeted intervention of either formal TIS or matched sham stimulation 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.

Study Overview

• Status: Recruiting
• Conditions: Parkinson Disease (PD)
• Intervention / Treatment: Device: Temporal Interference Stimulation; Device: Temporal Interference Stimulation

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Liu Hanjun; Phone Number: +86 15920175118; Email: lhanjun@mail.sysu.edu.cn
• Study Contact Backup: Name: Dan Zi; Phone Number: +8618922465578; Email: 925343654@qq.com

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Recruiting
      • Department of Rehabilitation Medicine, The First Affiliated Hospital, Sun Yat-sen University
      • Contact: Liu Hanjun; Phone Number: +86 15920175118; Email: lhanjun@mail.sysu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Idiopathic Parkinson's disease diagnosed by neurologists according to the Movement Disorder Society Clinical Diagnostic Criteria;
2. Hoehn and Yahr stage 1.5-3.0;
3. Stable levodopa-based antiparkinsonian medication for at least 4 weeks before enrolment, with no planned medication change during the trial period;
4. Ability to walk independently;
5. Ability to understand and follow study instructions and complete the required assessments, with no severe cognitive impairment as screened by the Montreal Cognitive Assessment and/or Mini-Mental State Examination according to prespecified thresholds;
6. Willingness to participate and provide written informed consent.

Exclusion Criteria:

1. Any contraindication to MRI or tTIS, including claustrophobia or ferromagnetic intracranial or subcutaneous implants;
2. Significant systemic disease that could increase study risk or interfere with trial participation;
3. Neurological disorders other than Parkinson's disease;
4. Major psychiatric disorder or severe depression or anxiety;
5. History of deep brain stimulation surgery;
6. Inability or unwillingness to complete all interventions and assessments.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active Stimulation Group; Participants diagnosed with Parkinson's disease in the active stimulation group will receive sequential bilateral subthalamic nucleus (STN) temporal interference electrical stimulation therapy twice daily, with each session lasting 40 minutes and a rest interval of at least 1 hour between treatments. The stimulation target is the bilateral subthalamic nucleus, with individualized electrode placement and current intensity determined via personalized modeling based on each patient's magnetic resonance imaging (MRI) data. For the stimulation protocol, a unified carrier frequency of 2000 Hz is adopted for bilateral STN intervention. Specifically, TI stimulation with an envelope frequency of 130 Hz is delivered to the STN contralateral to the patient's most symptomatic side, while TI stimulation with an envelope frequency of 60 Hz is administered to the STN ipsilateral to the patient's most symptomatic side.	Device: Temporal Interference Stimulation; Sequential bilateral subthalamic nucleus (STN) temporal interference electrical stimulation (sham 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. Sham stimulation uses two identical high frequencies (2000 Hz and 2000 Hz) to eliminate the therapeutic interference effect, matching all other procedural details to the active stimulation arm.; Other Names: TIS; TI; tTIS; TI Stimulation; Transcranial Temporal Interference Electrical Stimulation; Device: Temporal Interference Stimulation; Sequential 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.; Other Names: TIS; TI; tTIS; TI Stimulation; Transcranial Temporal Interference Stimulation
Sham Comparator: Sham Stimulation Group; Participants diagnosed with Parkinson's disease in the sham stimulation group will follow an identical stimulation protocol to the active stimulation group (twice daily, 40 minutes per session, bilateral STN targeting via personalized MRI modeling), except that two identical high frequencies (2000 Hz and 2000 Hz) are applied to eliminate the therapeutic interference effect, serving as a sham control condition.	Device: Temporal Interference Stimulation; Sequential bilateral subthalamic nucleus (STN) temporal interference electrical stimulation (sham 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. Sham stimulation uses two identical high frequencies (2000 Hz and 2000 Hz) to eliminate the therapeutic interference effect, matching all other procedural details to the active stimulation arm.; Other Names: TIS; TI; tTIS; TI Stimulation; Transcranial Temporal Interference Electrical Stimulation; Device: Temporal Interference Stimulation; Sequential 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.; Other Names: TIS; TI; tTIS; TI Stimulation; Transcranial Temporal Interference Stimulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From enrollment to 1 month after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From enrollment to 1 month after treatment
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.	From the enrollment to 1 month after treatment
BOLD-fMRI	Functional MRI is used to acquire BOLD data. BOLD signals reflect regional brain activity and functional connectivity. This measure evaluates brain function and structural connectivity associated with motor and cognitive performance.	From the enrollment to 1 month after treatment
Phonation duration	Phonation duration refers to the continuous time of voluntary phonation. This indicators is used to objectively evaluate the functional status of the subjects' vocal system. Abnormalities in phonation duration 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.	From the enrollment to 1 month after treatment
Diffusion Tensor Imaging（DTI）	Functional MRI is used to acquire Diffusion Tensor Imaging（DTI) data. DTI characterizes white matter microstructural integrity and fiber tract organization. This measure evaluates brain function and structural connectivity associated with motor and cognitive performance.	From the enrollment to 1 month after treatment
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.	From the enrollment to 1 month after treatment
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.	From the enrollment to 1 month after treatment
Fundamental frequency (F₀)	Fundamental frequency (F₀) range of subjects' phonation is measured using Praat software. Fundamental frequency range is the interval between the minimum and maximum F₀ (unit: Hz) during phonation, reflecting the variability of voice pitch. This indicators is used to objectively evaluate the functional status of the subjects' vocal system. Abnormalities in F₀ range 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.	From the enrollment to 1 month after treatment
Range of center of pressure (COP) sway	Center of pressure (COP) sway range 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 the maximum displacement range of COP deviation under both single-task and dual-task standing states. This indicator objectively assesses postural stability and balance regulation ability on different surfaces; abnormal increases indicate deteriorated postural control, aiding evaluation of balance disorder severity and intervention effectiveness.	From the enrollment to 1 month after treatment
Path of center of pressure (COP) sway	Center of pressure (COP) sway path 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 the total traveling path length of COP movement under both single-task and dual-task standing states. This indicator objectively reflects the complexity and stability of postural adjustment during standing on different surfaces; abnormal increases indicate inefficient balance control and postural instability, aiding evaluation of balance disorder severity and intervention effectiveness.	From the enrollment to 1 month after treatment
Area of center of pressure (COP) sway	Center of pressure (COP) sway area 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 the planar enclosed area covered by continuous COP movement under both single-task and dual-task standing states. This indicator objectively evaluates the overall stability of standing posture and anti-interference ability on different surfaces; abnormal increases represent expanded postural sway range and impaired balance function, aiding evaluation of balance disorder severity and intervention effectiveness.	From the enrollment to 1 month after treatment
Timed Up and Go (TUG) Test Time	The time consumed by subjects to complete the standard Timed Up and Go (TUG) test is recorded as the evaluation outcome. During the test, subjects are required to finish a series of standardized movements including standing up from a chair, straight walking, turning around, and sitting back down independently. This indicator objectively assesses basic walking ability, functional mobility and gross motor control ability of subjects; prolonged completion time indicates impaired walking and mobility function, aiding the evaluation of motor dysfunction severity and intervention effectiveness.	From the enrollment to 1 month after treatment
Dual-Task Timed Up and Go (Dual-Task TUG) Test Time	The time consumed by subjects to complete the dual-task Timed Up and Go (TUG) test is recorded as the evaluation outcome. During the dual-task test, subjects are required to finish the entire standard TUG motor sequence while simultaneously performing continuous serial subtraction of 7 from random numbers within 100, which imposes additional cognitive load during walking. This indicator comprehensively reflects subjects' dual-task execution ability, integrating walking mobility and cognitive-motor coordination capacity. Increased completion time represents declined dual-task processing efficiency and compromised gait stability under cognitive interference, aiding the evaluation of comprehensive motor-cognitive function and intervention effectiveness.	From the enrollment to 1 month after treatment

Collaborators and Investigators

• Sponsor: Ke Dong, MD

Study record dates

Study Major Dates

• Study Start (Estimated): July 20, 2026
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: July 19, 2026
• First Submitted That Met QC Criteria: July 19, 2026
• First Posted (Actual): July 23, 2026

Study Record Updates

• Last Update Posted (Actual): July 23, 2026
• Last Update Submitted That Met QC Criteria: July 19, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Synucleinopathies; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; Movement Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Parkinson Disease
• Other Study ID Numbers: Nos.82402971

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No