A Double-blinded, Randomized, Parallel-group, Superiority Study to Explore the Neuroprotective Effects of Long-term Transcutaneous Auricular Vagus Nerve Stimulation(taVNS) in Early Parkinson's Disease(PD) Patients
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Sponsor
- Enrollment
- 12
- Locations
- 1
- Primary Endpoint
- MDS-UPDRS-Ⅲ
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 55 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Age 55-75 years.
- •Clinically diagnosed Idiopathic Parkinson's disease patients according to the 2016 Chinese diagnostic criteria for Parkinson's disease.
- •Hoehn and Yahr (H&Y) stage ≤ 2.5 at medication initiation.
- •Parkinson's disease duration ≤ 3 years.
- •Receiving standard anti-Parkinson's disease medication treatment.
Exclusion Criteria
- •Patients with cognitive impairment (MMSE < 24 and/or MoCA < 26) or mental illnesses, or those unable to cooperate for other reasons.
- •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-
- •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.
- •Previous treatment with vagus nerve stimulation.
- •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.
- •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.
- •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.
- •Previous history of stroke or intracranial mass lesions.
- •Patients with existing or potential cardiovascular diseases.
- •Ophthalmic diseases affecting eye movements.
- •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).
- •Severe organic diseases, such as late-stage tumors, with a life expectancy of less than 2 years.
- •Concurrent participation in other clinical trials.
- •Inability to receive the required treatment and follow-up due to geographic reasons.
- •Any subject with an upper limb UPDRS tremor score of 3 or higher.
- •Patients with a history of PD-related freezing episodes or falls.
Arms & Interventions
Standard anti-Parkinson's disease medication treatment + taVNS 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.
Each Parkinson's disease patient will receive one 30-minute stimulation session per day(at least 5 days per week) for 270 consecutive days.
Intervention: taVNS real stimulation (Device)
Standard anti-Parkinson's disease medication treatment + taVNS sham stimulation
For the sham stimulation group, two modified point electrodes will deliver stimulation to the earlobes.Each Parkinson's disease patient will receive one 30-minute stimulation session per day(at least 5 days per week) for 270 consecutive days.
Intervention: taVNS sham stimulation (Device)
Outcomes
Primary Outcomes
MDS-UPDRS-Ⅲ
Time Frame: 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)
Time Frame: baseline, 180±7 days, 360±7 days, 540±7 days，570±7 days
Used to measure progression of early Parkinson's disease.
Secondary Outcomes
- Scales: MDS-UPDRS-II(baseline,30±3 days,90±5 days,180±7 days, 360±7 days, 540±7 days，570±7 days)
- Step Length、Stride Length、Stride Velocity and Step Length Variability(baseline,180±7 days, 360±7 days, 540±7 days，570±7 days)
- Scales: H&Y stage(baseline,30±3 days,90±5 days,180±7 days, 360±7 days, 540±7 days，570±7 days)
Investigators
Kezhong Zhang
Professor
The First Affiliated Hospital with Nanjing Medical University