Immediate Effects of External Trigeminal Nerve Stimulation on Motor Dysfunction in Parkinson's Disease

NCT07656129 | Not Yet Recruiting DMC

• 1 other identifier: LSS-K-2026-012-01
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Parkinson's Disease (PD)

Keywords

external Trigeminal Nerve Stimulation; Parkinson's Disease; Motor dysfunction

Outcome Measures

Primary Outcomes (3)

• 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.

  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.

Secondary Outcomes (3)

• 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.

• 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.

• 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.

Other Outcomes (4)

• Hoehn and Yahr Scale

  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]

  Throughout the experimental session, approximately 2.5-3 hours

• Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III

  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.

Study Arms (3)

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.

Device: external Trigeminal Nerve Stimulation, eTNS

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.

Device: external Trigeminal Nerve Stimulation, eTNS

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).

Device: external Trigeminal Nerve Stimulation, eTNS

Interventions

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.

Also known as: Anti-parkinson's disease drugs

120Hz-eTNS; 40Hz-eTNS; sham-eTNS

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Hoehn and Yahr stage 1-5 in the medication ON state.
• Mini-Mental State Examination (MMSE) score \>24.
• Stable antiparkinsonian medication for at least 1 month before the trial.
• No history of orthopedic or musculoskeletal disorders, and no other conditions that may affect balance or gait, such as ophthalmologic disorders.
• 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.
• Age between 40 and 80 years.
• Ability to cooperate with all assessments and eTNS treatment, and provision of written informed consent.

You may not qualify if:

• Secondary parkinsonism or atypical parkinsonian syndromes.
• Current use of anticholinergic medications.
• Contraindications to non-invasive electrical neuromodulation.
• Previous eTNS treatment within the past 6 months.
• Severe neurological, renal, cardiovascular, hepatic, or other major systemic diseases.
• Inability to complete clinical assessments or refusal to provide written informed consent.

Sponsors & Collaborators

• Zhengli Di: lead

Study Sites (1)

Xi'an Central Hospital, Department of Neurology

Xi'an, Shaanxi, 710000, China

Location

MeSH Terms

Conditions

Parkinson Disease; Neurologic Manifestations

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Rong Li, PhD candidate

CONTACT

+86 15529957876; 15529957876@163.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director of the Neurology Department

Model Details: Each patient will complete three conditions in a single session in randomized order

Study Record Dates

• First Submitted: June 8, 2026
• First Posted: June 18, 2026
• Study Start: June 15, 2026
• Primary Completion: July 15, 2026
• Study Completion: July 15, 2026
• Last Updated: June 18, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)