Accelerated Temporal Interference Stimulation on Bilateral Subthalamic Nucleus for Parkinson's Disease and Secondary Parkinson's Syndrome

NCT07568067 — Not applicable, Recruiting, 60 participants, Ke Dong, MD

ClinicalTrials Daily · Areas · Conditions · Drugs · Sponsors ·

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

Registry	NCT07568067
Status	Recruiting
Phase	Not applicable
Study type	Interventional; randomized, parallel, masking: double, treatment
Enrollment	60 (Estimated)
Sponsor	Ke Dong, MD (Other); collaborators: Sun Yat-sen University
Conditions	Parkinson Disease, Parkinson Disease, Secondary
Interventions	Temporal Interference Stimulation (Device)
Dates	start 2026-04-21, primary completion 2026-08-30 (estimated), completion 2026-10-30 (estimated), first posted 2026-05-05, last updated 2026-07-21
Locations	1 site in China

-Summary

This clinical trial will evaluate the efficacy of accelerated Temporal Interference Stimulation (TIS) as a therapeutic intervention for individuals diagnosed with Parkinson's disease or secondary Parkinson's syndrome. Accelerated TIS will be delivered targeting the bilateral subthalamic nuclei of the brain. 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 speech performance 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 four-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 accelerated 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 accelerated TIS, with no valid neuromodulation therapeutic effect generated. Identical random grouping, intervention arrangement and controlled research design will be fully implemented in eligible subjects diagnosed with secondary Parkinson's syndrome. Rigorous controlled grouping design will ensure objective, verifiable data support for verifying the actual intervention efficacy of accelerated 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 accelerated 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

Expand all sections · Collapse all

+Arms and interventions

Arm	Type	Interventions	Description
Active Stimulation Group-Parkinson's disease	Experimental	Device: Temporal Interference Stimulation	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. The active stimulation uses two distinct high frequencies (2000 Hz and 2130 Hz) to generate a therapeutic interference field.
Sham Stimulation Group-Parkinson's disease	Sham comparator	Device: Temporal Interference Stimulation	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.
Active Stimulation Group- secondary Parkinson's syndrome	Experimental	Device: Temporal Interference Stimulation	Participants diagnosed with secondary Parkinson's syndrome 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. The active stimulation uses two distinct high frequencies (2000 Hz and 2130 Hz) to generate a therapeutic interference field.
Sham Stimulation Group- secondary Parkinson's syndrome	Sham comparator	Device: Temporal Interference Stimulation	Participants diagnosed with secondary Parkinson's syndrome 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.

Temporal Interference Stimulation (Device), also known as TIS, TI Stimulation, TI, cTIS, Transcranial 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. Active stimulation uses two distinct high frequencies (2000 Hz and 2130 Hz) to generate a therapeutic interference field.
Temporal Interference Stimulation (Device), also known as TI, TIS, TI Stimulation, Transcranial Temporal Interference Electrical Stimulation, cTIS: 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.

+Outcome measures

Primary outcomes

The score of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS-III) [From enrollment to 1 month after treatment]: 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.

Secondary outcomes

The scores of Mini-BESTest [From enrollment to 1 month after treatment]: 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 [From the enrollment to 1 month after treatment]: 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 [From the enrollment to 1 month after treatment]: 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 [From the enrollment to 1 month after treatment]: Center of pressure (COP) sway velocity of subjects on stable and unstable surfaces is measured via a balance board, recording COP movement speed during standing. 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.
BOLD-fMRI [From the enrollment to 1 month after treatment]: 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.
Phonation duration [From the enrollment to 1 month after treatment]: 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.
Fundamental frequency (F₀) [From the enrollment to 1 month after treatment]: 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.
Range of center of pressure (COP) sway [From the enrollment to 1 month after treatment]: Center of pressure (COP) sway range of subjects on stable and unstable surfaces is measured via a balance board, recording COP movement maximum horizontal displacement during standing. 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.
Diffusion Tensor Imaging（DTI） [From the enrollment to 1 month after treatment]: 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.

+Eligibility

Sex: All, ages: any to 85 Years

Inclusion Criteria:

1. Confirmed diagnosis of idiopathic Parkinson's disease or secondary parkinson's syndrome ; Hoehn-Yahr stage 1.5-3.
2. Ability to walk independently.
3. Ability to follow instructions, with no cognitive impairment.
4. Patient and their family agree to cooperate with treatment and provide written informed consent.

Exclusion Criteria:

1. Claustrophobia or presence of metallic implants precluding MRI examination and evaluation.
2. Severe dysfunction of vital organs including heart, lung, liver, kidney, etc.
3. Complicated with other neurological diseases such as cerebral infarction.
4. Presence of mental illness, severe depression, anxiety, etc., which may affect the accuracy of study results.
5. History of deep brain stimulation (DBS) surgery.
6. Patients unable or unwilling to cooperate with scale assessments.
7. Aged over 80 years old.

+Locations (1)

Facility	City	Country	Status
Department of Rehabilitation Medicine, The First Affiliated Hospital, Sun Yat-sen University	Guangzhou, Guangdong	China	Recruiting