A Randomized Double-Blind Active-Controlled Crossover Trial of Respiratory-Gated Versus Non-Gated Transcutaneous Auricular Vagus Nerve Stimulation for the Treatment of Motor and Non-Motor Symptoms in Parkinson's Disease
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Not specified
- Sponsor
- Not provided
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- Unified Parkinson's Disease Rating Scale Part III (UPDRS-III)
- Status
- Enrolling By Invitation
- Last Updated
- 4 months ago
Overview
Brief Summary
The goal of this clinical trial is to compare the effects of different modes and frequencies of transcutaneous auricular vagus nerve stimulation (taVNS) on motor and non-motor symptoms in people with Parkinson's disease. The main questions it aims to answer are:
Which mode and frequency of taVNS is most effective in improving motor or non-motor symptoms? Are there any side effects or safety concerns with different taVNS frequencies? Researchers will compare three types of taVNS: 25 Hz non-expiratory gated, 25 Hz expiratory gated, and 100 Hz expiratory gated stimulation.
Participants will:
Receive each type of taVNS in three 2-week cycles, with 2-month breaks between cycles Undergo neuropsychological assessments, imaging, eye-tracking, and biological sample collection before and after each cycle.
Detailed Description
This study employs a three-cycle crossover design to compare the effects of three different modes and frequencies of transcutaneous auricular vagus nerve stimulation (taVNS). The interventions include: 25 Hz non-expiratory gated taVNS, 25 Hz expiratory gated taVNS, and 100 Hz expiratory gated taVNS. Participants will be randomly assigned to one of three groups, with each group receiving a different intervention during each cycle, lasting 2 weeks per cycle. A 2-month washout period will be implemented between cycles to eliminate any carryover effects.The study design will include neuropsychological assessments, imaging, eye-tracking data collection, and biological specimen collection before and after each intervention.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age: 40 years or older.
- •Confirmed diagnosis of Parkinson's disease (PD) per the United Kingdom Brain Bank Criteria by a neurologist specialized in movement disorders.
- •Participants must be on a stable dose of all medications for at least 2 weeks, with no planned adjustments to anti-PD medications for the next 3 months.
- •In the second version of the Non-Motor Symptoms Scale (NMSS-2) for Parkinson's disease, a score of ≥1 is assigned to either question 4 or question
- •Participants must be in good mental health and capable of completing behavioral tests and transcutaneous auricular vagus nerve stimulation.
Exclusion Criteria
- •Mini-Mental State Examination (MMSE) score \<
- •History of head injury, stroke, or other neurological disorders.
- •Includes implanted cardiac pacemakers post-DBS operation, local infections, ear loss, or metal implants at the stimulation site.
- •Current use of nonsteroidal anti-inflammatory drugs (NSAIDs) or corticosteroids.
- •Inability to complete follow-up assessments.
Outcomes
Primary Outcomes
Unified Parkinson's Disease Rating Scale Part III (UPDRS-III)
Time Frame: Baseline;2 weeks; 10 weeks; 12 weeks;20 weeks;22weeks
The Unified Parkinson's Disease Rating Scale, Part III (UPDRS-III) is the gold standard, clinician-administered motor examination for Parkinson's disease. It is a semi-quantitative scale comprising 18 items assessing core motor features-tremor, rigidity, bradykinesia, and postural/gait dysfunction. Each item is scored from 0 (normal) to 4 (severe), with a total possible score of 108. As the primary endpoint in clinical trials, it objectively quantifies motor disability severity and treatment response.
Non-Motor Symptoms Scale, Second Version (NMSS-2)
Time Frame: Baseline;2 weeks; 10 weeks; 12 weeks;20 weeks;22weeks
The NMSS-2 is a comprehensive, clinician-administered tool designed to assess the range and severity of non-motor symptoms in individuals with Parkinson's disease. It covers multiple domains including sleep disturbances, mood, cognition, gastrointestinal symptoms, urinary dysfunction, and other non-motor manifestations. This second version of the scale provides an updated and refined assessment framework to capture the broad impact of non-motor symptoms on patients' quality of life.
Secondary Outcomes
- Apathy Motivation Index (AMI)(Baseline;2 weeks; 10 weeks; 12 weeks;20 weeks;22weeks)
- Apathy Evaluation Scale (AES)(Baseline;2 weeks; 10 weeks; 12 weeks;20 weeks;22weeks)
- Fatigue Scale-14 (FS-14)(Baseline;2 weeks; 10 weeks; 12 weeks;20 weeks;22weeks)
- Pittsburgh Sleep Quality Index (PSQI)(Baseline;2 weeks; 10 weeks; 12 weeks;20 weeks;22weeks)
- REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ)(Baseline;2 weeks; 10 weeks; 12 weeks;20 weeks;22weeks)
- Hamilton Anxiety Rating Scale (HAMA)(Baseline;2 weeks; 10 weeks; 12 weeks;20 weeks;22weeks)
- Hamilton Depression Rating Scale (HAMD-17)(Baseline;2 weeks; 10 weeks; 12 weeks;20 weeks;22weeks)
- Epworth Sleepiness Scale (ESS)(Baseline;2 weeks; 10 weeks; 12 weeks;20 weeks;22weeks)