Respiratory-gated Transcutaneous Auricular Vagus Nerve Stimulation for Improving Apathy in Parkinson's Disease

November 17, 2025 updated by: WANG KAI, Anhui Medical University

Respiratory-gated Transcutaneous Auricular Vagus Nerve Stimulation for Improving Apathy in Parkinson's Disease: A Randomized, Double-blind, Sham-controlled Trial

The goal of this clinical trial is to learn whether 100HZ respiratory-gated vagus nerve stimulation (RAVANS) can improve the non-motor symptoms in people with Parkinson's disease (PD). It will also learn the safety of 100HZ RAVANS. The main questions it aims to answer are:

Can 100HZ RAVANS improve apathy in people with PD? Did the participants have any side effects or safety issues when undergoing 100HZ RAVANS? Researchers compared 100HZ RAVANS with sham stimulation (low-dose stimulation of the same site and treatment parameters) to see if 100HZ RAVANS could improve non-motor symptoms in patients with PD.

Participants will:

Receive 100HZ RAVANS or sham stimulation for 2 weeks. Neuropsychological assessment, imaging and biological sample collection were conducted before and after the entire cycle.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This study employs a double-blind, sham-controlled design to further validate the effects of 100Hz RAVANS on apathy . Patients were randomized into real or sham stimulation groups. Both groups will receive RAVANS once daily, with each session lasting 30 minutes, for a total duration of two weeks. The study design will include neuropsychological assessments, imaging, and biological specimen collection before and after the entire cycle.

Study Type

Interventional

Enrollment (Estimated)

60

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Anhui
      • Hefei, Anhui, China, 230022
        • Recruiting
        • Cognitive Neuropsychology Lab Anhui Medical University
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Meet the diagnostic criteria for idiopathic Parkinson's disease (based on the MDS Clinical Diagnostic Criteria for Parkinson's Disease (2015 version)).
  2. Patients with Apathy Motivation Index (AMI) score >1.7.
  3. All PD patients must be on stable, standardized medication regimens with no adjustments to medications for at least 1 month prior to the study and throughout the study period.
  4. Demonstrate good compliance and adherence, capable of completing behavioral tests and taVNS therapy.
  5. Mini-Mental State Examination (MMSE) score ≥22.
  6. Meet safety criteria for MRI screening.

Exclusion Criteria:

  1. Prior brain MRI/CT showing focal brain lesions or severe white matter disease (Fazekas grade 3 or higher).
  2. Secondary parkinsonism (e.g., vascular parkinsonism, drug-induced parkinsonism).
  3. History of severe traumatic brain injury, neurosurgery, or deep brain stimulation (DBS) therapy.
  4. Personal history of epilepsy, unexplained loss of consciousness, or current use of anticonvulsant medications for seizure control.
  5. Diagnosis of neuropsychiatric disorders other than Parkinson's disease.
  6. Current use of non-steroidal anti-inflammatory drugs (NSAIDs) or Non-benzodiazepine GABA receptor agonist drug or anticholinergics or corticosteroids, or history of substance abuse or drug addiction.
  7. Participation in any clinical trial within the past 3 months.
  8. Severe systemic comorbidities (e.g., hepatic/renal failure, arrhythmias, organic heart disease).
  9. Pregnant/lactating women or subjects (including males) planning pregnancy within 6 months.
  10. Contraindications to taVNS, such as cardiac pacemakers, post-DBS surgery, or auricular pathologies (e.g., tympanic membrane perforation).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Active respiratory-gated transcutaneous auricular vagus nerve stimulation (RAVANS)
Participants will receive active RAVANS daily for 2 week.
Other: Active RAVANS
Real RAVANS was performed on the cymba conchae of left ear in the vicinity of the auricular branch vagus nerve according to the Participant's respiratory rhythm. Stimulation parameters: frequency = 100 Hz; pulse width = 200 us, once a day, 30 minutes each time, one second of stimulation occurs during exhalation.
Other Names:
  • RAVANS
Sham Comparator: Sham RAVANS
Participants will receive sham RAVANS daily for 2 week.
Other: Sham RAVANS
Sham RAVANS was performed on on the cymba conchae of left ear according to the Participant's respiratory rhythm. Stimulation parameters: frequency = 100 Hz; pulse width = 200 us, once a day, 30 minutes each time, one second of stimulation occurs during exhalation and the interval between stimulus is 29 seconds.
Other Names:
  • RAVANS

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Apathy Motivation Index (AMI)
Time Frame: baseline; 2 weeks; 6weeks; 8weeks; 10 weeks
The AMI is used to assess levels of apathy across behavioral, emotional, and cognitive domains. It provides a comprehensive measure of motivation deficits.
baseline; 2 weeks; 6weeks; 8weeks; 10 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Non-Motor Symptoms Scale, Second Version (NMSS-2)
Time Frame: baseline; 2 weeks; 6weeks; 8weeks; 10 weeks
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.
baseline; 2 weeks; 6weeks; 8weeks; 10 weeks
AMI subscales
Time Frame: baseline; 2 weeks; 6weeks; 8weeks; 10 weeks
AMI has three subscale dimensions including behavioral activation, social motivation and emotional sensitivity.
baseline; 2 weeks; 6weeks; 8weeks; 10 weeks
Epworth Sleepiness Scale (ESS)
Time Frame: baseline; 2 weeks; 10 weeks
The ESS is a widely used self-assessment questionnaire designed to measure daytime sleepiness. It was developed by Dr. Murray Johns in 1991 and is commonly employed in clinical and research settings to evaluate excessive daytime sleepiness , which is often associated with sleep disorders like obstructive sleep apnea ,narcolepsy, or insomnia.
baseline; 2 weeks; 10 weeks
Fatigue Scale-14 (FS-14)
Time Frame: baseline; 2 weeks; 10 weeks
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.
baseline; 2 weeks; 10 weeks
Pittsburgh Sleep Quality Index (PSQI)
Time Frame: baseline; 2 weeks; 10 weeks
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.
baseline; 2 weeks; 10 weeks
REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ)
Time Frame: baseline; 2 weeks; 10 weeks
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.
baseline; 2 weeks; 10 weeks
The Unified Parkinson's Disease Rating Scale, Part III (UPDRS-III)
Time Frame: baseline; 2 weeks; 10 weeks
The UPDRS-III is a standardized clinical assessment tool used to evaluate the motor symptoms of Parkinson's disease (PD). It is part of the broader UPDRS, which is the most widely accepted scale for assessing the severity and progression of PD. Below is a detailed explanation.
baseline; 2 weeks; 10 weeks
The Neuropsychiatric Inventory (NPI)
Time Frame: baseline; 2 weeks; 10 weeks
The Neuropsychiatric Inventory (NPI) is a standardized tool used to assess neuropsychiatric symptoms (such as hallucinations, depression, agitation, etc.) in patients with dementia.
baseline; 2 weeks; 10 weeks
The Hamilton Anxiety Rating Scale (HAMA)
Time Frame: baseline; 2 weeks; 10 weeks
The Hamilton Anxiety Rating Scale (HAMA) is a clinician-administered assessment tool widely used in clinical practice to evaluate the severity of anxiety symptoms
baseline; 2 weeks; 10 weeks
The Hamilton Depression Rating Scale (HAMD)
Time Frame: baseline; 2 weeks; 10 weeks
The Hamilton Depression Rating Scale (HAMD) is a clinician-administered assessment tool commonly used in clinical practice to evaluate the severity of depressive symptoms.
baseline; 2 weeks; 10 weeks
Heart Rate Variability (HRV)
Time Frame: baseline everyday; during the intervention everyday
Heart Rate Variability (HRV) is a physiological indicator that assesses the function of the autonomic nervous system (ANS) by analyzing subtle variations in heartbeat intervals (R-R intervals). The vagus nerve serves as the primary pathway of the parasympathetic nervous system. Transcutaneous auricular vagus nerve stimulation (taVNS) enhances parasympathetic nerve activity by stimulating the auricular branch of the vagus nerve. HRV is a critical metric for evaluating the efficacy of this regulatory effect.Each day before treatment, a 5-minute resting HRV is recorded, followed by a 30-minute HRV recording during the intervention.
baseline everyday; during the intervention everyday
Behavioral performance and computational parameters in an effort-based decision-making task
Time Frame: baseline; 2 weeks
The Effort-Based Decision-Making Task is an experimental paradigm used to investigate how individuals weigh effort costs against task rewards under differenct conditions. Behavioral and computational indexes are calculated across varying levels of effort and reward.The main indicators are the selection rate and accuracy rate under different levels of effort and reward
baseline; 2 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Anhui Medical University

Investigators

  • Principal Investigator: Kai Wang, Ph.D., Anhui Medical University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 1, 2025

Primary Completion (Estimated)

May 1, 2027

Study Completion (Estimated)

May 1, 2028

Study Registration Dates

First Submitted

May 19, 2025

First Submitted That Met QC Criteria

August 11, 2025

First Posted (Actual)

August 12, 2025

Study Record Updates

Last Update Posted (Actual)

November 19, 2025

Last Update Submitted That Met QC Criteria

November 17, 2025

Last Verified

May 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PD-TaVNS-RCT

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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