Curative Effect and Mechanism of Transcutaneous Auricular Vagus Nerve Stimulation on Sleep Disorders of PD

Study on the Efficacy and Mechanism of Transcutaneous Auricular Vagus Nerve Stimulation in the Treatment of Sleep Disorders in Parkinson's Disease

This study is a double-blind comparative study examining the curative effect and mechanism of the transcutaneous auricular vagus nerve stimulation treatment on non-motor symptoms of Parkinson's disease patients. The investigators hypothesize that treatment using transcutaneous auricular vagus nerve stimulation will improve the non-motor symptoms, such as improving sleep, and improve cortical activity simultaneously in Parkinson's disease patients.

Study Overview

• Status: Completed
• Conditions: Parkinson Disease
• Intervention / Treatment: Device: Transcutaneous auricular vagus nerve stimulation (real stimulation); Device: Transcutaneous auricular vagus nerve stimulation (sham stimulation)

Detailed Description

Patients in the Experimental group underwent fourteen consecutive daily sessions of transcutaneous auricular vagus nerve stimulation (taVNS, twice daily, 30 minutes each time), whereas patients in the sham stimulation group underwent fourteen consecutive daily sessions of sham taVNS. Assessments of motor and non-motor symptoms, cortical activity (using Functional near-infrared spectroscopy) and blood indicators were performed three times: at baseline, one day post intervention, fourteen days post intervention.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Jiang Su
    • Nanjing, Jiang Su, China, 210029
      • The First Affiliated Hospital of Nanjing Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

(i) right-handed individuals aged 45-80 years; (ii) met the diagnostic criteria for idiopathic PD and had been stable on medication for at least one month; (iii) met the diagnostic criteria for insomnia according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and insomnia had to have lasted for at least six months, with Pittsburgh sleep quality index (PSQI) scores >7; (iv) no history of medication that might affect the study, such as sleeping pills or antidepressants, that is, the PSQI hypnotic medication score of 0; (v) clear consciousness, basic communication skills and cooperation in all assessments and treatments; (vi) The patients agreed to participate in the study and signed an informed consent form.

Exclusion Criteria:

(i) those with concomitant cognitive dysfunction, such as Montreal cognitive assessment (MoCA) <23; (ii) those with secondary Parkinson's syndrome or Parkinson's superimposed syndrome; (iii) those with severe cardiac, pulmonary, hepatic, renal, or concomitant malignancies or a history of previous brain surgery; (iv) those with contraindications to taVNS interventions; (v) those with severe psychiatric disorders; (vi) Insomnia not caused by PD, such as frequent (two times per week) nighttime use of sedative medications (including sedative antidepressants), untreated restless legs syndrome, night-shift work or other occupations that result in abnormal sleep patterns, insomnia associated with dopamine therapy, and other reversible causes of insomnia identified by the baseline clinical interview.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: active transcutaneous auricular vagus nerve stimulatio; For Experimental Arm, active transcutaneous auricular vagus nerve stimulation, Patients underwent fourteen consecutive daily sessions of taVNS.	Device: Transcutaneous auricular vagus nerve stimulation (real stimulation); Transcutaneous auricular vagus nerve stimulation was conducted by transcutaneous electrical stimulation therapy instrument to the cymba conchae of left ear in the vicinity of the auricular branch vagus nerve. Stimulation parameters: frequency = 20/4 Hz; pulse width = 200 μs, twice a day, 30 minutes each time.
Sham Comparator: sham transcutaneous auricular vagus nerve stimulation; For sham transcutaneous auricular vagus nerve stimulation arm, Sham Comparator, patients underwent fourteen consecutive daily sessions of sham-taVNS (the electrodes were fixed at the left earlobe with the same stimulation parameters).	Device: Transcutaneous auricular vagus nerve stimulation (sham stimulation); Transcutaneous auricular vagus nerve stimulation was conducted by transcutaneous electrical stimulation therapy instrument to the left earlobe. Stimulation parameters: frequency = 20/4 Hz; pulse width = 200 μs, twice a day, 30 minutes each time.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in sleep quality, sleep efficiency of patients	Pittsburgh sleep quality index (PSQI) was used to evaluate the sleep quality of participants in the past month. It consists of 19 self-evaluation and 5 other evaluation items. The total score range is 0-21, with higher scores indicating poorer sleep quality.	Assessed at baseline, one day post intervention, fourteen days post intervention.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in ΔHbO2 concentration in the brain cortex	The ΔHbO2 concentration in the brain cortex will be recorded in oxyhemoglobin.	Assessed at baseline, one day post intervention.
Changes of sleep quality scale	Non-motor symptoms such as sleep disorders were evaluated by Parkinson's disease sleep scale-2 (PDSS-2). PDSS-2 is an improved version of PDSS used to screen for common types of sleep disorders in Parkinson's disease patients. The minimum and maximum values of the non-motor part of the PDSS-2 Scale are 0 and 60. A higher score means a worse outcome.	Assessed at baseline, one day post intervention, fourteen days post intervention.
Changes of Rapid-eye-movement Sleep Behavior Disorder scale	Rapid-eye-movement Sleep Behavior Disorder Screening Questionnaire (RBDSQ) was used to assess the behavior disorder of multiple eye movement sleep. The minimum and maximum values of the non-motor part of the RBDSQ Scale are 0 and 13. A higher score means a worse outcome.	Assessed at baseline, one day post intervention, fourteen days post intervention.
The motor part of the Unified Parkinson's Disease Rating Scale	The measure mainly reflects the overall severity of Parkinson's disease motor symptoms. The minimum and maximum values of the motor part of the Unified Parkinson's Disease Rating Scale are 0 and 108. A higher score means a worse outcome.	Assessed at baseline, one day post intervention, fourteen days post intervention.
Plasma indicators	5ml of the patient's elbow vein blood was collected and centrifuged after standing and stratified. The blood plasma was collected and frozen at - 20 ℃ for testing. Detection of changes in plasma ghrelin levels.	Assessed at baseline, one day post intervention, fourteen days post intervention.
Epworth sleepiness scale (ESS)	The Epworth Sleepiness Scale, also known as the Epworth Daytime Sleepiness Scale, was developed by Johns MW to assess excessive daytime sleepiness. This scale has clinical significance: it can provide a semi-objective assessment of sleepiness. Scoring more than 6 out of 24 indicates drowsiness, more than 11 indicates excessive sleepiness, and more than 16 indicates dangerous sleepiness.	Assessed at baseline, one day post intervention.
Hamilton Depression Scale-24 (HAMD-24)	The Hamilton Depression Rating Scale is the most widely used instrument for clinical assessment of depressive states, effectively reflecting the severity of the condition. The total score ranges from 0 to 76 points, with lower scores indicating milder symptoms and higher scores signifying more severe conditions.	Assessed at baseline, one day post intervention.
Hamilton Anxiety Scale (HAMA)	The Hamilton Anxiety Scale is commonly used in clinical practice as a basis for diagnosing anxiety disorders and assessing their severity. The total score can be used to evaluate the severity of anxiety symptoms in patients with anxiety and depressive disorders, as well as to assess the effects of various pharmacological and psychological interventions. According to data provided by the Chinese Scale Collaborative Group: a total score ≥29 indicates possible severe anxiety; ≥21 confirms significant anxiety; ≥14 confirms the presence of anxiety; >7 suggests possible anxiety; and a score <7 indicates no anxiety symptoms.	Assessed at baseline, one day post intervention.
Montreal Cognitive Assessment (MoCA)	The Montreal Cognitive Assessment is an evaluation tool used for rapid screening of patients with mild cognitive impairment. The assessed cognitive domains include attention and concentration, executive function, memory, language, visuospatial skills, abstract thinking, as well as calculation and orientation. The total score of the scale is 30 points, with test results indicating a normal value of ≥26 points.	Assessed at baseline, one day post intervention.
Subjective sleep assessment	Using sleep logs to record participants' subjective sleep data, including subjective sleep quality scores，early morning refreshment scores, easy wake up scores, ease of falling asleep scores, and dreaming scores.	Assessed at baseline, one day post intervention, fourteen days post
Objective sleep assessment	Using MI wristbands for objective sleep assessment, including deep sleep time scores，night waking up times, light sleep duration, and the REM sleep duration.	Assessed at baseline, one day post intervention, fourteen days post

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital with Nanjing Medical University
• Collaborators: National Natural Science Foundation of China
• Investigators: Principal Investigator: Kezhong Zhang, The First Affiliated Hospital with Nanjing Medical University

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2022
• Primary Completion (Actual): August 8, 2023
• Study Completion (Actual): December 31, 2023

Study Registration Dates

• First Submitted: February 27, 2023
• First Submitted That Met QC Criteria: April 7, 2023
• First Posted (Actual): April 10, 2023

Study Record Updates

• Last Update Posted (Actual): June 11, 2025
• Last Update Submitted That Met QC Criteria: June 6, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Therapeutics; non-motor symptoms; nighttime insomnia
• Additional Relevant MeSH Terms: Synucleinopathies; Neurologic Manifestations; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurodegenerative Diseases; Movement Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Parkinson Disease; Sleep Wake Disorders
• Other Study ID Numbers: 2022-SR-519

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