Parkinson Disease, Idiopathic
Conditions
Keywords
Parkinson Disease, Idiopathic, Vagus Nerve Stimulation
Brief summary
This study is a randomized, double-blind, controlled trial exploring the effects of long-term taVNS intervention in patients with early-stage Parkinson's disease.
Detailed description
This study is a randomized, double-blind, controlled trial exploring the effects of long-term taVNS intervention in patients with early-stage Parkinson's disease, , aiming to investigate a novel therapeutic approach for delaying PD progression.
Interventions
DEVICEtaVNS real stimulation
For the real stimulation group, two modified point electrodes will deliver stimulation near the auricular branch of the vagus nerve in the left concha cymba. Stimulation parameters: frequency = 20 Hz; pulse width = 500 μs; continuous stimulation for 60 seconds, followed by a 10-second off period, repeated for 30 minutes.
DEVICEtaVNS sham stimulation
For the sham stimulation group, two modified point electrodes will deliver stimulation to the earlobes.Stimulation parameters: frequency = 20 Hz; pulse width = 500 μs; continuous stimulation for 60 seconds, followed by a 10-second off period, repeated for 30 minutes.
Sponsors
Kezhong Zhang
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
55 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Age 55-75 years. 2. Clinically diagnosed Idiopathic Parkinson's disease patients according to the 2016 Chinese diagnostic criteria for Parkinson's disease. 3. Hoehn and Yahr (H&Y) stage ≤ 2.5 at medication initiation. 4. Parkinson's disease duration ≤ 3 years. 5. Receiving standard anti-Parkinson's disease medication treatment.
Exclusion criteria
1. Patients with cognitive impairment (MMSE \< 24 and/or MoCA \< 26) or mental illnesses, or those unable to cooperate for other reasons. 2. Use of neuroprotective medications within 90 days prior to baseline, including monoamine oxidase B inhibitors (rasagiline, selegiline), certain dopamine receptor agonists (ropinirole), and GLP-1 receptor agonists such as Exenatide and NLY-01. 3. Use of any medications that may affect dopamine metabolism and/or dopamine receptors within 90 days prior to baseline, including typical and atypical antipsychotics, metoclopramide, α-methyl-dopa, flunarizine, apomorphine, amphetamine derivatives, bupropion, buprenorphine, cocaine, meperidine, methamphetamine, norephedrine, phentermine, modafinil, methylphenidate, procyclidine, reserpine, phenylpropanolamine, or MAO-A inhibitors. 4. Previous treatment with vagus nerve stimulation. 5. MRI contraindications (e.g., claustrophobia unresponsive to comfort or low-dose anxiolytics, dental implants) or MRI scans indicating clinically significant abnormalities in the brain, including but not limited to past hemorrhages or infarcts \> 1 cm³ or \> 3 lacunar infarcts. 6. Contraindications for taVNS, such as patients with cardiac pacemakers or a history of DBS surgery, or those planning surgery during the trial; ear conditions, such as tympanic membrane perforation. 7. Atypical or secondary Parkinsonian syndromes, including but not limited to those caused by trauma, brain tumors, infections, cerebrovascular diseases, or other neurological disorders, or symptoms confirmed by the investigator as drug, chemical, or toxin-related. 8. Previous history of stroke or intracranial mass lesions. 9. Patients with existing or potential cardiovascular diseases. 10. Ophthalmic diseases affecting eye movements. 11. Any neurological disorders other than Parkinsonian motor symptoms that interfere with gait or balance (e.g., chronic pain) or musculoskeletal injuries (e.g., fractures, stroke sequelae). 12. Severe organic diseases, such as late-stage tumors, with a life expectancy of less than 2 years. 13. Concurrent participation in other clinical trials. 14. Inability to receive the required treatment and follow-up due to geographic reasons. 15. Any subject with an upper limb UPDRS tremor score of 3 or higher. 16. Patients with a history of PD-related freezing episodes or falls.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| MDS-UPDRS-Ⅲ | baseline, 180±7 days, 360±7 days, 540±7 days，570±7 days | Used to evaluate the motor function. |
| Free water in the posterior substantia nigra (DTI) | baseline, 180±7 days, 360±7 days, 540±7 days，570±7 days | Used to measure progression of early Parkinson's disease. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Scales: MDS-UPDRS-II | baseline,30±3 days,90±5 days,180±7 days, 360±7 days, 540±7 days，570±7 days | Used to evaluate quality of life of PD. |
| Step Length、Stride Length、Stride Velocity and Step Length Variability | baseline,180±7 days, 360±7 days, 540±7 days，570±7 days | Used to assess the patient's gait disturbances，including the Step Length、Stride Length、Stride Velocity and Step Length Variability |
| Scales: H&Y stage | baseline,30±3 days,90±5 days,180±7 days, 360±7 days, 540±7 days，570±7 days | Used to evaluate the stage of PD. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with the following Serum biomarkers: | baseline,180±7 days, 360±7 days, 540±7 days，570±7 days | Brain-Derived Neurotrophic Factor (BDNF): Measurement: Concentration (measured in ng/mL). Glial Fibrillary Acidic Protein (GFAP): Measurement: Concentration (measured in ng/mL). Neurofilament Light Chain (NFL): Measurement: Concentration (measured in pg/mL). Tau Protein: Measurement: Concentration (measured in pg/mL). Tumor Necrosis Factor Alpha (TNF-α): Measurement: Concentration (measured in pg/mL). Interleukin-6 (IL-6): Measurement: Concentration (measured in pg/mL). Interleukin-1 Beta (IL-1β): Measurement: Concentration (measured in pg/mL). |
| Movement Disorder Society Unified Parkinson's Disease Rating Scale - Part I (MDS-UPDRS-I) | baseline,30±3 days,90±5 days,180±7 days, 360±7 days, 540±7 days，570±7 days | .Measurement: Score (range: 0-52; higher score indicates worse non-motor function). |
| Non-Motor Symptoms Scale (NMSS) | baseline,30±3 days,90±5 days,180±7 days, 360±7 days, 540±7 days，570±7 days | Measurement: Score (range: 0-100; higher score indicates more severe non-motor symptoms). |
| Activities of Daily Living (ADL) Scale | baseline,30±3 days,90±5 days,180±7 days, 360±7 days, 540±7 days，570±7 days | Measurement: Score (range: 0-100; higher score indicates greater independence). |
| Apathy Scale (AS) | baseline,30±3 days,90±5 days,180±7 days, 360±7 days, 540±7 days，570±7 days | Measurement: Score (range: 0-42; higher score indicates greater apathy). |
| Rapid Eye Movement Sleep Behavior Disorder Questionnaire (RBDSQ) | baseline,30±3 days,90±5 days,180±7 days, 360±7 days, 540±7 days，570±7 days | Measurement: Score (range: 0-25; higher score indicates more severe symptoms). |
| Eye-Tracking Technology | baseline,180±7 days, 360±7 days, 540±7 days，570±7 days | Fixation Duration: The length of time the gaze remains on a single point. Saccade Velocity: The speed of eye movements between fixations. Scan Path: The trajectory of eye movements during visual exploration |
| Montreal Cognitive Assessment (MoCA) | baseline,30±3 days,90±5 days,180±7 days, 360±7 days, 540±7 days，570±7 days | Measurement: Score (range: 0-30; higher score indicates better cognitive function). |
| Hopkins Verbal Learning Test - Revised (HVLT-R) | baseline,30±3 days,90±5 days,180±7 days, 360±7 days, 540±7 days，570±7 days | Measurement: Score (varies by subscale; higher score indicates better verbal memory). |
| Judgment of Line Orientation (JLO) | baseline,30±3 days,90±5 days,180±7 days, 360±7 days, 540±7 days，570±7 days | Measurement: Score (range: 0-30; higher score indicates better visual-spatial abilities). |
| Letter-Number Sequencing (LNS) | baseline,30±3 days,90±5 days,180±7 days, 360±7 days, 540±7 days，570±7 days | Measurement: Score (range: 0-30; higher score indicates better working memory). |
| Symbol Digit Modalities Test (SDMT) | baseline,30±3 days,90±5 days,180±7 days, 360±7 days, 540±7 days，570±7 days | Measurement: Score (varies based on response time; higher score indicates faster processing speed). |
| Levodopa Equivalent Dose (LED) | baseline,30±3 days,90±5 days,180±7 days, 360±7 days, 540±7 days，570±7 days | Measurement: Dose (measured in mg; higher dose indicates greater medication requirement). |
| Epworth Sleepiness Scale (ESS) | baseline,30±3 days,90±5 days,180±7 days, 360±7 days, 540±7 days，570±7 days | Measurement: Score (range: 0-24; higher score indicates greater daytime sleepiness). |
| Electroencephalogram (EEG) | baseline,180±7 days, 360±7 days, 540±7 days，570±7 days | Measurement: Brain wave activity (measured in microvolts, µV). |
| MRI | baseline,180±7 days, 360±7 days, 540±7 days，570±7 days | T1-weighted Imaging: Measurement: Structural brain volume (measured in cubic centimeters, cm³). BOLD fMRI: Measurement: Blood oxygen level-dependent signals (measured in percentage change). Diffusion Tensor Imaging (DTI): Fractional Anisotropy (FA): Measurement: FA values (unitless, scale from 0 to 1). Mean Diffusivity (MD): Measurement: MD values (measured in mm²/s). NM-MRI: Measurement: Neurochemical markers (unit as appropriate). Iron-sensitive MRI: Quantitative Susceptibility Mapping (QSM): Measurement: Susceptibility values (measured in parts per million, ppm). Susceptibility Weighted Imaging (SWI): Measurement: Signal intensity (unitless). R2\*: Measurement: Relaxation rate (measured in Hz). |
| Hamilton Anxiety Scale (HAMA) | baseline,30±3 days,90±5 days,180±7 days, 360±7 days, 540±7 days，570±7 days | Measurement: Score (range: 0-56; higher score indicates greater anxiety). |
| Hamilton Depression Rating Scale - 24 items (HAMD-24) | baseline,30±3 days,90±5 days,180±7 days, 360±7 days, 540±7 days，570±7 days | Measurement: Score (range: 0-76; higher score indicates greater depression severity). |
Countries
China
Contacts
Primary ContactKezhong Zhang, Professor
Outcome results
None listed