Clinical trial NCT06665113: Neuroprotective Effects of Long-term TaVNS in Early Parkinson's Disease Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Parkinson Disease, Idiopathic
Keywords: Parkinson Disease, Idiopathic
Vagus Nerve Stimulation
Lead sponsor: The First Affiliated Hospital with Nanjing Medical University
Sponsor class: OTHER
First posted: 2024-10-30
Enrollment: 12
Sex: ALL
Minimum age (years): 55
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: MDS-UPDRS-Ⅲ
timeFrame: baseline, 180±7 days, 360±7 days, 540±7 days，570±7 days
measure: Free water in the posterior substantia nigra (DTI)
timeFrame: baseline, 180±7 days, 360±7 days, 540±7 days，570±7 days
Secondary outcomes:
measure: Scales: MDS-UPDRS-II
timeFrame: baseline,30±3 days,90±5 days,180±7 days, 360±7 days, 540±7 days，570±7 days
measure: Step Length、Stride Length、Stride Velocity and Step Length Variability
timeFrame: baseline,180±7 days, 360±7 days, 540±7 days，570±7 days
measure: Scales: H&Y stage
timeFrame: baseline,30±3 days,90±5 days,180±7 days, 360±7 days, 540±7 days，570±7 days
Other outcomes:
measure: Eye-Tracking Technology
timeFrame: baseline,180±7 days, 360±7 days, 540±7 days，570±7 days
measure: Electroencephalogram (EEG)
timeFrame: baseline,180±7 days, 360±7 days, 540±7 days，570±7 days
measure: MRI
timeFrame: baseline,180±7 days, 360±7 days, 540±7 days，570±7 days
measure: Number of participants with the following Serum biomarkers:
timeFrame: baseline,180±7 days, 360±7 days, 540±7 days，570±7 days
measure: Movement Disorder Society Unified Parkinson's Disease Rating Scale - Part I (MDS-UPDRS-I)
timeFrame: baseline,30±3 days,90±5 days,180±7 days, 360±7 days, 540±7 days，570±7 days
measure: Non-Motor Symptoms Scale (NMSS)
timeFrame: baseline,30±3 days,90±5 days,180±7 days, 360±7 days, 540±7 days，570±7 days
measure: Activities of Daily Living (ADL) Scale
timeFrame: baseline,30±3 days,90±5 days,180±7 days, 360±7 days, 540±7 days，570±7 days
measure: Hamilton Anxiety Scale (HAMA)
timeFrame: baseline,30±3 days,90±5 days,180±7 days, 360±7 days, 540±7 days，570±7 days
measure: Hamilton Depression Rating Scale - 24 items (HAMD-24)
timeFrame: baseline,30±3 days,90±5 days,180±7 days, 360±7 days, 540±7 days，570±7 days
measure: Apathy Scale (AS)
timeFrame: baseline,30±3 days,90±5 days,180±7 days, 360±7 days, 540±7 days，570±7 days
measure: Rapid Eye Movement Sleep Behavior Disorder Questionnaire (RBDSQ)
timeFrame: baseline,30±3 days,90±5 days,180±7 days, 360±7 days, 540±7 days，570±7 days
measure: Epworth Sleepiness Scale (ESS)
timeFrame: baseline,30±3 days,90±5 days,180±7 days, 360±7 days, 540±7 days，570±7 days
measure: Montreal Cognitive Assessment (MoCA)
timeFrame: baseline,30±3 days,90±5 days,180±7 days, 360±7 days, 540±7 days，570±7 days
measure: Hopkins Verbal Learning Test - Revised (HVLT-R)
timeFrame: baseline,30±3 days,90±5 days,180±7 days, 360±7 days, 540±7 days，570±7 days
measure: Judgment of Line Orientation (JLO)
timeFrame: baseline,30±3 days,90±5 days,180±7 days, 360±7 days, 540±7 days，570±7 days
measure: Letter-Number Sequencing (LNS)
timeFrame: baseline,30±3 days,90±5 days,180±7 days, 360±7 days, 540±7 days，570±7 days
measure: Symbol Digit Modalities Test (SDMT)
timeFrame: baseline,30±3 days,90±5 days,180±7 days, 360±7 days, 540±7 days，570±7 days
measure: Levodopa Equivalent Dose (LED)
timeFrame: baseline,30±3 days,90±5 days,180±7 days, 360±7 days, 540±7 days，570±7 days
Locations:
city: Nanjing
country: China
facility: The First Affiliated Hospital with Nanjing Medical University
state: Jiangsu
Study officials:
affiliation: The First Affiliated Hospital with Nanjing Medical University
name: Kezhong Zhang, Professor
role: PRINCIPAL_INVESTIGATOR
References: