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Parkinson's disease (PD), the most common movement disorder, is characterized by motor symptoms including tremor, rigidity, bradykinesia, and postural instability. These symptoms substantially impair quality of life and increase the risk of falls, disability, and accidental injury, representing a major therapeutic challenge.
External trigeminal nerve stimulation (eTNS), a non-invasive neuromodulation technique, has shown promising potential in PD and other movement disorders. A clinical study published in 2017 suggested that trigeminal nerve stimulation may contribute to the alleviation of motor symptoms in patients with PD. In 2023, the U.S. Food and Drug Administration cleared the Portable Neuromodulation Stimulator (PoNS) as an adjunctive treatment for gait impairment caused by multiple sclerosis; the lingual nerve is a branch of the mandibular division of the trigeminal nerve. In the same year, experimental evidence showed that trigeminal nerve stimulation could activate intracranial dopaminergic neurons and modulate dopamine release in mice. These findings suggest substantial potential for eTNS in modulating motor dysfunction in PD, although high-level clinical evidence remains lacking.
This randomized, within-subject study will evaluate the immediate effects of eTNS at different stimulation frequencies on motor dysfunction in patients with PD. Gait parameters will be quantitatively assessed using the IDEEA gait system, together with the MDS-Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS Part III), Tinetti Gait Scale, and Hoehn and Yahr Scale.
This within-subject study comprises three 20-min stimulation conditions: 120-Hz eTNS, 40-Hz eTNS, and sham stimulation. Each patient with Parkinson's disease will complete all conditions in a single session in randomized order. Instrumented gait analysis, together with motor and gait rating scales, will be used to quantify immediate post-stimulation changes in gait and motor function relative to baseline.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 40Hz-eTNS | Active Comparator | 40-Hz eTNS: frequency,40Hz; pulse width, 250 μs; duty cycle, 30 s on/30 s off; total stimulation duration, 20 min. |
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| 120Hz-eTNS | Active Comparator | 120-Hz eTNS: frequency,120Hz; pulse width, 250 μs; duty cycle, 30 s on/30 s off; total stimulation duration, 20 min. |
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| sham-eTNS | Sham Comparator | Sham eTNS used a double-ramp paradigm with the same parameters as the 120-Hz condition(frequency,120Hz; pulse width, 250 μs; total stimulation duration, 20 min.), but current was delivered only at stimulation onset (0-15 s) and midway through the session (15 s at 10 min). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| external Trigeminal Nerve Stimulation, eTNS | Device | The experiment will be conducted in the MED-ON state, consistently 1-2 h after administration of antiparkinsonian medication. Baseline gait and motor function assessments will first be performed, followed by three randomized eTNS stimulation sessions. Gait will be assessed after each stimulation session, and motor function scales will be reassessed after completion of all experimental conditions. |
| Measure | Description | Time Frame |
|---|---|---|
| Dual-Task Cost (DTC) | This is a within-subject study. Instrumented gait parameters and clinical rating scales will be assessed at baseline, followed by eTNS stimulation in randomized order under the 120-Hz, 40-Hz, and sham conditions. After each eTNS condition, instrumented gait parameters will be collected during walking tasks. Clinical rating scales will be additionally assessed after the final stimulation condition.Dual-task cost will be calculated as: [(single-task gait speed - dual-task gait speed) / single-task gait speed] × 100%.DTC reflects the reduction in walking performance under dual-task conditions relative to single-task conditions. A decrease in DTC after eTNS indicates reduced dual-task interference during walking, suggesting that eTNS may reduce dual-task gait cost in patients with PD. | DTC will be assessed at baseline and after each randomized eTNS condition during walking tasks, using the IDEEA inertial sensor based gait analysis system. |
| Mean Gait Speed（m/s） | This is a within-subject study. Instrumented gait parameters and clinical rating scales will be assessed at baseline, followed by eTNS stimulation in randomized order under the 120-Hz, 40-Hz, and sham conditions. After each eTNS condition, instrumented gait parameters will be collected during walking tasks. Clinical rating scales will be additionally assessed after the final stimulation condition. Mean gait speed will be directly obtained from the IDEEA system, which uses inertial sensors to quantitatively monitor gait during walking tasks in patients with PD. | Mean gait speed will be assessed at baseline and after each randomized eTNS condition during walking tasks, using the IDEEA inertial sensor-based gait analysis system. |
| Mean Stride Length (m) | This is a within-subject study. Instrumented gait parameters and clinical rating scales will be assessed at baseline, followed by eTNS stimulation in randomized order under the 120-Hz, 40-Hz, and sham conditions. After each eTNS condition, instrumented gait parameters will be collected during walking tasks. Clinical rating scales will be additionally assessed after the final stimulation condition. Mean stride length will be directly obtained from the IDEEA system, which uses inertial sensors to quantitatively monitor gait during walking tasks in patients with PD. |
| Measure | Description | Time Frame |
|---|---|---|
| stride frequency（steps/min） | This is a within-subject study. Instrumented gait parameters and clinical rating scales will be assessed at baseline, followed by eTNS stimulation in randomized order under the 120-Hz, 40-Hz, and sham conditions. After each eTNS condition, instrumented gait parameters will be collected during walking tasks. Clinical rating scales will be additionally assessed after the final stimulation condition.Stride frequency will be recorded as directly generated by the IDEEA system.Improvement in stride frequency after eTNS suggests potential improvement in walking rhythm and gait control in patients with PD. |
| Measure | Description | Time Frame |
|---|---|---|
| Hoehn and Yahr Scale | This is a within-subject study. Instrumented gait parameters and clinical rating scales will be assessed at baseline, followed by eTNS stimulation in randomized order under the 120-Hz, 40-Hz, and sham conditions. After each eTNS condition, instrumented gait parameters will be collected during walking tasks. Clinical rating scales will be additionally assessed after the final stimulation condition.The Hoehn and Yahr scale ranges from 1 to 5 in this study. Higher stages indicate more advanced disease and greater motor disability. It is a clinical staging system used to assess the overall severity of Parkinson's disease based on the distribution of motor symptoms, postural instability, walking ability, and functional disability. A higher stage indicates more severe disease. A decrease in Hoehn and Yahr scale after eTNS would suggest improvement in overall motor function and disease severity. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Rong Li, PhD candidate | Contact | +86 15529957876 | 15529957876@163.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Xi'an Central Hospital, Department of Neurology | Xi'an | Shaanxi | 710000 | China |
Individual participant data will not be shared because the informed consent documents and ethics approval do not specifically include permission for public or external sharing of individual-level participant data. Aggregate study results may be shared through publications or presentations.
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP_ICF | Yes | Yes | Yes | Study Protocol, Statistical Analysis Plan, and Informed Consent Form | Mar 3, 2026 | Jun 8, 2026 | Prot_SAP_ICF_000.pdf |
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| ID | Term |
|---|---|
| D010300 | Parkinson Disease |
| D009461 | Neurologic Manifestations |
| ID | Term |
|---|---|
| D020734 | Parkinsonian Disorders |
| D001480 | Basal Ganglia Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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Each patient will complete three conditions in a single session in randomized order
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| Mean stride length will be assessed at baseline and after each randomized eTNS condition during walking tasks, using the IDEEA inertial sensor-based gait analysis system. |
| It will be assessed at baseline and after each randomized eTNS condition during walking tasks, using the IDEEA inertial sensor-based gait analysis system. |
| Double-support phase percentage（%） | This is a within-subject study. Instrumented gait parameters and clinical rating scales will be assessed at baseline, followed by eTNS stimulation in randomized order under the 120-Hz, 40-Hz, and sham conditions. After each eTNS condition, instrumented gait parameters will be collected during walking tasks. Clinical rating scales will be additionally assessed after the final stimulation condition.Double-support phase percentage will be calculated as: (double-support time / gait cycle time) × 100%. A higher Double-support phase percentage value generally indicates greater reliance on double-limb support to maintain stability, suggesting more cautious gait, impaired dynamic balance, and increased fall risk. A decrease in double-support phase percentage after eTNS suggests reduced dependence on double-limb support and potential improvement in gait stability and dynamic balance in patients with PD. | It will be assessed at baseline and after each randomized eTNS condition during walking tasks, using the IDEEA inertial sensor-based gait analysis system. |
| gait symmetry index（%） | This is a within-subject study. Instrumented gait parameters and clinical rating scales will be assessed at baseline, followed by eTNS stimulation in randomized order under the 120-Hz, 40-Hz, and sham conditions. After each eTNS condition, instrumented gait parameters will be collected during walking tasks. Clinical rating scales will be additionally assessed after the final stimulation condition.The symmetry index will be calculated as: |left-side gait parameter - right-side gait parameter| / [0.5 × (left-side gait parameter + right-side gait parameter)] × 100%.The symmetry index reflects the degree of difference between left- and right-side gait parameters and is used to evaluate bilateral gait symmetry. A higher value indicates greater asymmetry, whereas a lower value indicates better gait symmetry. A decrease in the symmetry index after eTNS suggests improved bilateral gait symmetry in patients with PD. | It will be assessed at baseline and after each randomized eTNS condition during walking tasks, using the IDEEA inertial sensor-based gait analysis system. |
| The scale will be administered twice: once at baseline before the experiment and once after completion of all eTNS stimulation conditions and walking tasks, namely at the end of the experiment. |
| Incidence of eTNS-Related Adverse Reactions [Safety and Tolerability] | Adverse reactions related to eTNS will be recorded throughout the experimental session, including local skin numbness, tingling, itching, redness at the electrode site, headache, dizziness, or any other discomfort reported by the participant or observed by the investigator. The number and percentage of participants experiencing eTNS-related adverse reactions will be reported. | Throughout the experimental session, approximately 2.5-3 hours |
| Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III | This is a within-subject study. Instrumented gait parameters and clinical rating scales will be assessed at baseline, followed by eTNS stimulation in randomized order under the 120-Hz, 40-Hz, and sham conditions. After each eTNS condition, instrumented gait parameters will be collected during walking tasks. Clinical rating scales will be additionally assessed after the final stimulation condition. Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III(MDS-UPDRS III) is a clinician-rated motor examination scale used to assess the severity of motor signs in Parkinson's disease, including rigidity, bradykinesia, tremor, gait, posture, and postural stability. The score ranges from 0 to 132, with each item rated from 0 to 4. Higher scores indicate more severe motor impairment.A decrease in the MDS-UPDRS Part III score after eTNS indicates improvement in motor function. | The scale will be administered twice: once at baseline before the experiment and once after completion of all eTNS stimulation conditions and walking tasks, namely at the end of the experiment. |
| Tinetti Gait Assessment | This is a within-subject study. Instrumented gait parameters and clinical rating scales will be assessed at baseline, followed by eTNS stimulation in randomized order under the 120-Hz, 40-Hz, and sham conditions. After each eTNS condition, instrumented gait parameters will be collected during walking tasks. Clinical rating scales will be additionally assessed after the final stimulation condition.The Tinetti Gait Assessment score ranges from 0 to 12. Higher scores indicate better gait performance and stability.The Tinetti Gait Assessment evaluates gait performance during walking, including gait initiation, step length and height, step symmetry, step continuity, walking path, trunk stability, and walking stance. A lower score indicates poorer gait function and greater gait instability, whereas a higher score indicates better gait function. An increase in the Tinetti Gait Assessment score after eTNS suggests improvement in gait function in patients with PD. | The scale will be administered twice: once at baseline before the experiment and once after completion of all eTNS stimulation conditions and walking tasks, namely at the end of the experiment. |
| D009422 | Nervous System Diseases |
| D009069 | Movement Disorders |
| D000080874 | Synucleinopathies |
| D019636 | Neurodegenerative Diseases |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |