Parkinson's Disease (PD)
Conditions
Keywords
external Trigeminal Nerve Stimulation, Parkinson's Disease, Motor dysfunction
Brief summary
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.
Interventions
DEVICEexternal Trigeminal Nerve Stimulation, eTNS
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.
Sponsors
Zhengli Di
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Intervention model description
Each patient will complete three conditions in a single session in randomized order
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Patients with idiopathic Parkinson's disease diagnosed by two neurologists, according to the Chinese diagnostic criteria for Parkinson's disease formulated in 2020 by the Chinese Parkinson's Disease and Movement Disorders Society based on the MDS Clinical Diagnostic Criteria for Parkinson's disease. 2. Hoehn and Yahr stage 1-5 in the medication ON state. 3. Mini-Mental State Examination (MMSE) score \>24. 4. Stable antiparkinsonian medication for at least 1 month before the trial. 5. No history of orthopedic or musculoskeletal disorders, and no other conditions that may affect balance or gait, such as ophthalmologic disorders. 6. No history of epilepsy, intracranial tumors, or other neurological disorders; no severe psychiatric disorders, such as schizophrenia; and no long-term use of antipsychotic medications. 7. Age between 40 and 80 years. 8. Ability to cooperate with all assessments and eTNS treatment, and provision of written informed consent.
Exclusion criteria
1. Secondary parkinsonism or atypical parkinsonian syndromes. 2. Current use of anticholinergic medications. 3. Contraindications to non-invasive electrical neuromodulation. 4. Previous eTNS treatment within the past 6 months. 5. Severe neurological, renal, cardiovascular, hepatic, or other major systemic diseases. 6. Inability to complete clinical assessments or refusal to provide written informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dual-Task Cost (DTC) | DTC will be assessed at baseline and after each randomized eTNS condition during walking tasks, using the IDEEA inertial sensor based gait analysis system. | 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. |
| Mean Gait Speed（m/s） | 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. | 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 Stride Length (m) | 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. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| stride frequency（steps/min） | It will be assessed at baseline and after each randomized eTNS condition during walking tasks, using the IDEEA inertial sensor-based gait analysis system. | 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. |
| Double-support phase percentage（%） | It will be assessed at baseline and after each randomized eTNS condition during walking tasks, using the IDEEA inertial sensor-based gait analysis system. | 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. |
| gait symmetry index（%） | It will be assessed at baseline and after each randomized eTNS condition during walking tasks, using the IDEEA inertial sensor-based gait analysis system. | 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. |
Countries
China
Contacts
CONTACTRong Li, PhD candidate
Outcome results
None listed