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

NCT06642454 | Enrolling By Invitation

• 1 other identifier: PD-TaVNS-OPEN
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

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.

Conditions

Parkinson Disease; Apathy; Sleep Disorder; Motor Disorders; Mood Disorders

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  Baseline;2 weeks; 10 weeks; 12 weeks;20 weeks;22weeks

Secondary Outcomes (8)

• 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

Study Arms (3)

25 Hz non-expiratory gated taVNS

EXPERIMENTAL

25 Hz non-expiratory gated transcutaneous auricular vagus nerve stimulation

Other: Transcutaneous auricular vagus nerve stimulation

25 Hz expiratory gated taVNS

EXPERIMENTAL

25 Hz expiratory gated transcutaneous auricular vagus nerve stimulation

Other: Transcutaneous auricular vagus nerve stimulation

100 Hz expiratory gated taVNS

EXPERIMENTAL

100 Hz expiratory gated transcutaneous auricular vagus nerve stimulation

Other: Transcutaneous auricular vagus nerve stimulation

Interventions

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.

100 Hz expiratory gated taVNS; 25 Hz expiratory gated taVNS; 25 Hz non-expiratory gated taVNS

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Anhui Medical University: lead

Study Sites (2)

Cognitive Neuropsychology Lab Anhui Medical University

Hefei, Anhui, 230022, China

Location

Cognitive Neuropsychology Lab Anhui Medical University

Hefei, Anhui, China

Location

MeSH Terms

Conditions

Parkinson Disease; Lethargy; Sleep Wake Disorders; Motor Disorders; Mood Disorders

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Neurobehavioral Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Mental Disorders

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head, Dept of Neurology & Medical Psychology, Director, Cognitive Neuropsychology Lab, PRC

Study Record Dates

• First Submitted: October 13, 2024
• First Posted: October 15, 2024
• Study Start: October 1, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): April 1, 2027
• Last Updated: December 19, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)