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

Official title

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.

Overview

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.

Interventions

• 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 frequenc
• 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 ot

Primary outcome measures

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

Secondary outcome measures (12)

• The scores of Mini-BESTest [Time frame: From enrollment to 1 month after treatment]
• 10-Meter Walk Test [Time frame: From the enrollment to 1 month after treatment]
• Voice intensity [Time frame: From the enrollment to 1 month after treatment]
• Velocity of center of pressure (COP) sway [Time frame: From the enrollment to 1 month after treatment]
• BOLD-fMRI [Time frame: From the enrollment to 1 month after treatment]
• Phonation duration [Time frame: From the enrollment to 1 month after treatment]
• Fundamental frequency (F₀) [Time frame: From the enrollment to 1 month after treatment]
• Range of center of pressure (COP) sway [Time frame: From the enrollment to 1 month after treatment]
• Path of center of pressure (COP) sway [Time frame: From the enrollment to 1 month after treatment]
• Area of center of pressure (COP) sway [Time frame: From the enrollment to 1 month after treatment]
• Diffusion Tensor Imaging（DTI） [Time frame: From the enrollment to 1 month after treatment]
• Timed Up and Go (TUG) Test Time [Time frame: From the enrollment to 1 month after treatment]

Eligibility criteria

Inclusion criteria

• 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;
• 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;
• Willingness to participate and provide written informed consent.

Exclusion criteria

• 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;
• History of deep brain stimulation surgery;
• Inability or unwillingness to complete all interventions and assessments.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

China · 1 center

• Department of Rehabilitation Medicine, The First Affiliated Hospital, Sun Yat-sen Universi — Guangzhou

Identifiers

NCT: NCT07721688 · Nos.82402971

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗