Parkinson DiseaseNCT06642454
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
A study testing Transcutaneous auricular vagus nerve stimulation in people with Parkinson Disease and Apathy, run by Anhui Medical University at 2 sites in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 40 to 80 years
- Conditions the study is for
- Parkinson Disease, Apathy, Sleep Disorder
- What is being tested?
- Transcutaneous auricular vagus nerve stimulation
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 2 sitesChina
- Study dates
- 1 Oct 2024to 1 Apr 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
China2 sites
Cognitive Neuropsychology Lab Anhui Medical University
Hefei, Anhui, 230022
Cognitive Neuropsychology Lab Anhui Medical University
Hefei, Anhui
About this study
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.
Read more
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.
Read the 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.
- Conditions
- Parkinson Disease, Apathy, Sleep Disorder, Motor Disorders, Mood Disorders
- Being tested
- Transcutaneous auricular vagus nerve stimulation
- Medical subject headings
- Parkinson Disease, Lethargy, Sleep Wake Disorders, Motor Disorders, Mood Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcutaneous auricular vagus nerve stimulationOther
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.
| Study group | Role | What they receive |
|---|---|---|
| 25 Hz non-expiratory gated taVNS | Experimental | 25 Hz non-expiratory gated transcutaneous auricular vagus nerve stimulation Receives: Other: Transcutaneous auricular vagus nerve stimulation |
| 25 Hz expiratory gated taVNS | Experimental | 25 Hz expiratory gated transcutaneous auricular vagus nerve stimulation Receives: Other: Transcutaneous auricular vagus nerve stimulation |
| 100 Hz expiratory gated taVNS | Experimental | 100 Hz expiratory gated transcutaneous auricular vagus nerve stimulation Receives: Other: Transcutaneous auricular vagus nerve stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Unified Parkinson's Disease Rating Scale Part III (UPDRS-III)
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.
Measured: Baseline;2 weeks; 10 weeks; 12 weeks;20 weeks;22weeks
Non-Motor Symptoms Scale, Second Version (NMSS-2)
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.
Measured: Baseline;2 weeks; 10 weeks; 12 weeks;20 weeks;22weeks
Secondary outcomes (8)
Apathy Motivation Index (AMI)
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.
Measured: Baseline;2 weeks; 10 weeks; 12 weeks;20 weeks;22weeks
Apathy Evaluation Scale (AES)
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.
Measured: Baseline;2 weeks; 10 weeks; 12 weeks;20 weeks;22weeks
Fatigue Scale-14 (FS-14)
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.
Measured: Baseline;2 weeks; 10 weeks; 12 weeks;20 weeks;22weeks
Pittsburgh Sleep Quality Index (PSQI)
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.
Measured: Baseline;2 weeks; 10 weeks; 12 weeks;20 weeks;22weeks
REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ)
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.
Measured: Baseline;2 weeks; 10 weeks; 12 weeks;20 weeks;22weeks
Hamilton Anxiety Rating Scale (HAMA)
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.
Measured: Baseline;2 weeks; 10 weeks; 12 weeks;20 weeks;22weeks
Hamilton Depression Rating Scale (HAMD-17)
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.
Measured: Baseline;2 weeks; 10 weeks; 12 weeks;20 weeks;22weeks
Epworth Sleepiness Scale (ESS)
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.
Measured: Baseline;2 weeks; 10 weeks; 12 weeks;20 weeks;22weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Oct 2024
- Study start1 Oct 2024
- Primary completion1 Dec 2026 (estimated)
- Study completion1 Apr 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Parkinson DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Anhui Medical University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, WANG KAI, Anhui Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06642454
- Sponsor's protocol ID
- PD-TaVNS-OPEN
- Status last verified
- Jun 2025
- First submitted
- 13 Oct 2024
- Last updated
- 19 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT06642454
- Acronym / sponsor ID
- PD-TaVNS-OPEN
- Conditions
- Parkinson Disease, Apathy, Sleep Disorder, Motor Disorders, Mood Disorders
- Study type
- Interventional
- Recruitment status
- Enrolling by invitation
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Anhui Medical UniversityUniversity, hospital or other
- Study start
- 1 Oct 2024 (actual)
- Primary completion
- 1 Dec 2026 (estimated)
- Study completion
- 1 Apr 2027 (estimated)
- First posted
- 15 Oct 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 25 Hz non-expiratory gated taVNS | Experimental | Other: Transcutaneous auricular vagus nerve stimulation25 Hz non-expiratory gated transcutaneous auricular vagus nerve stimulation |
| 25 Hz expiratory gated taVNS | Experimental | Other: Transcutaneous auricular vagus nerve stimulation25 Hz expiratory gated transcutaneous auricular vagus nerve stimulation |
| 100 Hz expiratory gated taVNS | Experimental | Other: Transcutaneous auricular vagus nerve stimulation100 Hz expiratory gated transcutaneous auricular vagus nerve stimulation |
Who may qualify
- Ages
- 40 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Transcutaneous auricular vagus nerve stimulationStimulation 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. | Other | 100 Hz expiratory gated taVNS, 25 Hz expiratory gated taVNS, 25 Hz non-expiratory gated taVNS |
Primary outcome
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.
8 secondary outcomes
Apathy Motivation Index (AMI)
Time frame: Baseline;2 weeks; 10 weeks; 12 weeks;20 weeks;22weeks
Apathy Evaluation Scale (AES)
Time frame: Baseline;2 weeks; 10 weeks; 12 weeks;20 weeks;22weeks
Fatigue Scale-14 (FS-14)
Time frame: Baseline;2 weeks; 10 weeks; 12 weeks;20 weeks;22weeks
Pittsburgh Sleep Quality Index (PSQI)
Time frame: Baseline;2 weeks; 10 weeks; 12 weeks;20 weeks;22weeks
REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ)
Time frame: Baseline;2 weeks; 10 weeks; 12 weeks;20 weeks;22weeks
Hamilton Anxiety Rating Scale (HAMA)
Time frame: Baseline;2 weeks; 10 weeks; 12 weeks;20 weeks;22weeks
Hamilton Depression Rating Scale (HAMD-17)
Time frame: Baseline;2 weeks; 10 weeks; 12 weeks;20 weeks;22weeks
Epworth Sleepiness Scale (ESS)
Time frame: Baseline;2 weeks; 10 weeks; 12 weeks;20 weeks;22weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Transcutaneous auricular vagus nerve stimulation in people with Parkinson Disease and Apathy, run by Anhui Medical University at 2 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: enrolling by invitation, as of the sponsor's last update on 19 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Unified Parkinson's Disease Rating Scale Part III (UPDRS-III) (time frame: Baseline;2 weeks; 10 weeks; 12 weeks;20 weeks;22weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Dec 2025; AzTrials last refreshed its copy on 26 Oct 2026.