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NCT Number: NCT06642454

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

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.

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Key information

Conditions

Parkinson Disease Apathy Basal Ganglia Diseases Brain Diseases Central Nervous System Diseases Lethargy Mental Disorders Mood Disorders Motor Disorders Movement Disorders Nervous System Diseases Neurobehavioral Manifestations Neurodegenerative Diseases Neurologic Manifestations Parkinsonian Disorders Pathological Conditions, Signs and Symptoms Signs and Symptoms Sleep Disorder Sleep Wake Disorders Synucleinopathies

Age range

40 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Cognitive Neuropsychology Lab Anhui Medical University, Hefei, Anhui, China

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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 8.
  • 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 <24.
  • 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.

Treatment and study plan

Transcutaneous Auricular Vagus Nerve Stimulation

Other

Stimulation Target: Left cymba conchae.

25 Hz Non-Expiratory Gated taVNS: Stimulation is delivered for 30 seconds at a frequency of 25 Hz, followed by a 30-second interval.

25 Hz Expiratory Gated taVNS: One second of stimulation occurs during exhalation at a frequency of 25 Hz.

100 Hz Expiratory Gated taVNS: One second of stimulation is administered during exhalation at a frequency of 100 Hz.

Primary outcomes

  1. 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.

  2. 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

  1. Apathy Motivation Index (AMI)

    Time frame: Baseline;2 weeks; 10 weeks; 12 weeks;20 weeks;22weeks

    Apathy Motivation Index (AMI) The AMI is used to assess levels of apathy across behavioral, emotional, and cognitive domains. It provides a comprehensive measure of motivation deficits.

  2. Apathy Evaluation Scale (AES)

    Time frame: Baseline;2 weeks; 10 weeks; 12 weeks;20 weeks;22weeks

    The AES is designed to evaluate the severity of apathy in individuals, focusing on the lack of motivation in behaviors, emotional responsiveness, and cognitive functioning.

  3. Fatigue Scale-14 (FS-14)

    Time frame: Baseline;2 weeks; 10 weeks; 12 weeks;20 weeks;22weeks

    The FS-14 is a self-report measure used to evaluate fatigue across physical and mental dimensions. It comprises 14 items that assess the severity and impact of fatigue on daily functioning.

  4. Pittsburgh Sleep Quality Index (PSQI)

    Time frame: Baseline;2 weeks; 10 weeks; 12 weeks;20 weeks;22weeks

    The PSQI is a standardized tool used to assess sleep quality and disturbances over a one-month time interval. It evaluates seven components of sleep, including subjective sleep quality, latency, duration, and daytime dysfunction.

  5. REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ)

    Time frame: Baseline;2 weeks; 10 weeks; 12 weeks;20 weeks;22weeks

    The RBDSQ is a diagnostic tool used to screen for REM Sleep Behavior Disorder (RBD), focusing on the presence of dream-enactment behaviors and other sleep-related symptoms.

  6. Hamilton Anxiety Rating Scale (HAMA)

    Time frame: Baseline;2 weeks; 10 weeks; 12 weeks;20 weeks;22weeks

    The HAMA is a clinician-administered scale designed to assess the severity of anxiety symptoms. It covers both psychological and somatic symptoms, providing a comprehensive evaluation of anxiety levels.

  7. Hamilton Depression Rating Scale (HAMD-17)

    Time frame: Baseline;2 weeks; 10 weeks; 12 weeks;20 weeks;22weeks

    The HAMD-17 is a widely used instrument for assessing the severity of depressive symptoms. It consists of 17 items that evaluate mood, physical symptoms, and cognitive disturbances associated with depression.

  8. Epworth Sleepiness Scale (ESS)

    Time frame: Baseline;2 weeks; 10 weeks; 12 weeks;20 weeks;22weeks

    The Epworth Sleepiness Scale (ESS) is a standardized self-report questionnaire measuring daytime sleep propensity. It lists eight common situations; respondents rate their likelihood of dozing (0-3) in each. The total score (0-24) quantifies subjective daytime sleepiness. It is a widely used screening tool for sleep disorders and treatment assessment.

Sponsors and collaborators

Lead sponsor

Anhui Medical University

Other

Registry information

Important dates

Study start
2024
Primary completion
2026
Study completion
2027
First posted
Oct 15, 2024
Registry last updated
Dec 19, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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