Subthalamic Nucleus (STN) Targeted Transcranial Temporal Interference Stimulation (TIS) Treats Parkinson's Disease (TIS-STN-PD1)

Tang Zhouping

Status: Not yet enrolling

Conditions: Parkinson Disease

Treatments: Device: NervioX-1000

Study type: Interventional

Funder types: Other

Identifiers

NCT07361250

202511129

Details and patient eligibility

About

This is a single-center, prospective, double-blind, randomized controlled trial to evaluate the efficacy and safety of transcranial temporal interference stimulation targeting the subthalamic nucleus in patients with Parkinson's disease. It plans to enroll 20 eligible participants who will be randomly assigned in a 1:1 ratio to either the active TIS stimulation group or the sham stimulation group.

Full description

Parkinson's disease is a progressive neurodegenerative disorder characterized by motor dysfunction.

Temporal Interference Stimulation (TIS) is a non-invasive deep brain stimulation technique. Its core principle involves placing two pairs of transcranial stimulation electrodes on the scalp surface, each delivering high-frequency currents with slight differences. Since the human cerebral cortex does not respond to high-frequency currents, when these two currents intersect in the deep brain (i.e., the target area), they generate a low-frequency interference wave-similar to tACS-with a frequency equal to the difference between the two currents. This enables selective modulation of deep brain regions while minimizing activation of the superficial cortex. Additionally, a breakthrough aspect of TIS is its ability to flexibly adjust the stimulation target location by modifying electrode positions and current ratios. This makes it highly suitable for future clinical applications in regulating deep brain nuclei and developing personalized diagnosis and treatment plans for Parkinson's disease (PD) patients. The technology offers a non-invasive method to alter neuronal activity in deep brain nuclei and has shown promise in improving PD motor symptoms in prior proof-of-concept studies, thereby providing a potential treatment for PD motor symptoms.

In animal models, TIS has been demonstrated to have the potential to modulate the activity of brain regions closely associated with PD motor symptoms, such as the subthalamic nucleus and globus pallidus. Preliminary clinical studies have shown that TIS stimulation of the unilateral STN in PD patients resulted in alleviation of motor symptoms such as tremor and bradykinesia before and after treatment . A recent exploratory study on TIS stimulation of the right GPi also confirmed that TIS is feasible and safe for alleviating mild PD motor symptoms, particularly bradykinesia and tremor. Compared to the right side, motor symptoms (especially bradykinesia) on the left side showed more significant improvement. PD patients with more severe bradykinesia and tremor before stimulation experienced greater improvement after TIS. Current research findings suggest that TIS has the potential to improve PD motor symptoms. However, in these two studies, some patients did not respond to TIS stimulation. Although preliminary data support the therapeutic potential of TIS for PD motor symptoms, there is still a lack of large-sample, randomized controlled, and systematic studies targeting different brain regions and parameter systems. Therefore, there is an urgent need to conduct standardized clinical trials to evaluate the optimal stimulation parameters, target selection, efficacy persistence, and safety of TIS, providing evidence-based support for its further promotion and application.

This study employs a single-center, prospective, randomized, double-blind, sham-controlled design to evaluate the efficacy and safety of TIS targeting the subthalamic nucleus in Parkinson's disease patients. The study protocol involves structural MRI scanning for all participants to establish individualized computational models, with neuronavigation techniques determining optimal electrode placement. Participants are randomized to either the active stimulation group (using 2000/2130 Hz dual-frequency configuration) or the sham control group (using 2000/2000 Hz configuration). All treatment sessions are conducted during patients' "ON" medication state, administered twice daily for 30 minutes over five consecutive days. Assessment is performed through blinded evaluation by raters unaware of group allocation using standardized scales at predetermined time points. The entire process follows structured data collection and safety monitoring protocols. This study aims to systematically evaluate the therapeutic effects and safety profile of TIS for motor symptoms in Parkinson's disease, providing an evidence base for the clinical application of this novel neuromodulation approach.

Enrollment: 20 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Age 18 years or older, no gender restriction;
2. Diagnosis of primary Parkinson's disease according to MDS criteria: specifically, the patient must (a) exhibit parkinsonism (bradykinesia + resting tremor/rigidity); (b) not meet any of the MDS absolute exclusion criteria; and (c) meet at least two MDS supportive criteria.
3. Disease duration ≥1 year, stable condition;
4. Hoehn-Yahr stage between 1.5 and 3, with a stable dose of levodopa or other dopaminergic medications for at least 4 weeks, responsive to levodopa-like medications, and no changes to the treatment regimen during the trial;
5. Good compliance, with the patient and family willing to participate in the clinical trial, voluntarily sign the informed consent form, attend regular treatments and follow-ups, and accurately complete evaluation tasks.

Exclusion criteria

1. Severe cognitive impairment, resulting in poor compliance due to dementia, and/or inability to sign the informed consent form;
2. History of severe psychiatric disorders, patients with a Hamilton Depression Scale (HAMD) score >24;
3. History of taking antipsychotic drugs, antidepressants, or other medications that may affect dopamine levels;
4. History of seizures within the last year or a family history of epilepsy;
5. Unable to complete MRI scanning (e.g., due to claustrophobia, or having metal implants in the body);
6. Patients with severe heart, liver, or kidney diseases, severe hypertension, and severe orthostatic hypotension that affect their health condition;
7. Patients with severe diabetes or severe cardio-cerebrovascular diseases that affect their health condition;
8. Diagnosed with malignant tumors;
9. Contraindications for non-invasive electrical stimulation, such as intracranial active implants (regardless of whether they are turned on) or passive implants that may affect electrical stimulation treatment, those who have undergone stereotactic deep brain stimulation or neurotomy, or have had any surgical procedures within the last six months that the investigator believes may affect this trial;
10. History of traumatic brain injury;
11. Pregnant women or women planning to become pregnant;
12. Subjects currently participating in other clinical trials or have participated in other clinical research within the last three months without reaching primary endpoints;
13. Patients deemed unsuitable to participate in this clinical study by the investigators.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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20 participants in 2 patient groups

Active TIS stimulation

Experimental group

Description:

Participants in this group will receive transcranial temporal interference stimulation targeting the subthalamic nucleus using a frequency pair of 2000 Hz and 2130 Hz. Stimulation will be delivered twice daily at the same time for 30 minutes per session over five consecutive days（only once on the 5th day）. Stimulation intensity will be individually titrated starting from a low level and gradually increased to the maximum tolerable level. All treatments will be administered during the participant's medication "on" state.

Treatment:

Device: NervioX-1000

Sham stimulation

Sham Comparator group

Description:

Participants in this group will receive sham stimulation using a frequency pair of 2000 Hz and 2000 Hz. Stimulation will be administered twice daily for 30 minutes per session over five consecutive days（only once on the 5th day） during the participant's medication "on" state, with current intensity individually titrated in the same manner as the active group. The sham protocol includes cutaneous sensation simulation during a 30-second ramp-up and ramp-down phase to maintain participant blinding, but does not generate an effective interference field in the deep brain target.

Treatment:

Device: NervioX-1000