A Comparative Open-Label Crossover Study of Respiratory-Gated Versus Non-Respiratory-Gated Transcutaneous Auricular Vagus Nerve Stimulation for the Treatment of Non-Motor Symptoms in Parkinson's Disease

Not Applicable

Recruiting

• Conditions: Fatigue; Parkinson Disease; Apathy; Sleep Disorder; Mood Disorders

• Registration Number: NCT06642454

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 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 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 Timeline

• Status Verified: 2024-09
• Study Start: 2024-10-01
• Study First Submitted: 2024-10-13
• Study First Submitted QC: 2024-10-13
• Study First Posted: 2024-10-15
• Last Update Submitted: 2025-04-17
• Last Update Posted: 2025-04-22
• Primary Completion: 2026-10-01
• Study Completion: 2027-04-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 30

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Primary Outcome Measures

Name	Time	Method
Non-Motor Symptoms Scale, Second Version (NMSS-2)	2 weeks; 6 weeks; 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.

Secondary Outcome Measures

Name	Time	Method
Pittsburgh Sleep Quality Index (PSQI)	2 weeks; 6 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.
REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ)	2 weeks; 6 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.
Hamilton Depression Rating Scale (HAMD-17)	2 weeks; 6 weeks; 10 weeks	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.
Hamilton Anxiety Rating Scale (HAMA)	2 weeks; 6 weeks; 10 weeks	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.
Apathy Motivation Index (AMI)	2 weeks; 6 weeks; 10 weeks	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.
Apathy Evaluation Scale (AES)	2 weeks; 6 weeks; 10 weeks	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.
Fatigue Scale-14 (FS-14)	2 weeks; 6 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.

Trial Locations

Locations (1)

Cognitive Neuropsychology Lab Anhui Medical University; 🇨🇳 Hefei, Anhui, China