The Efficacy and Safety of Transcutaneous Auricular Vagus Nerve Stimulation for Anxiety in PD

Study Overview
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Brief Summary
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This study is a double blind comparative study examining the effectiveness of the transcutaneous auricular vagus nerve stimulation treatment on Parkinson's disease patients with anxiety. The investigators hypothesize that taVNS will improve anxiety and cortical activity in Parkinson's disease patients with anxiety.

Detailed Description
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Participants in the Experimental group underwent fourteen consecutive daily sessions of transcutaneous auricular vagus nerve stimulation (taVNS, twice daily, 30 minutes each time) , whereas participants in the sham stimulation group underwent fourteen consecutive daily sessions of sham taVNS. Assessments of anxiety symptoms, motor symptoms were performed three times: at baseline, one day post intervention and 2 weeks post intervention. The cortical activity (using Functional near-infrared spectroscopy) were assessed at baseline, one day post intervention.

Official Title
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The Efficacy and Safety of Transcutaneous Auricular Vagus Nerve Stimulation for Anxiety in Parkinson's Disease

Conditions
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Parkinson Disease

Intervention / Treatment
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* Device: Active Transcutaneous auricular vagus nerve stimulation
* Device: Sham Transcutaneous auricular vagus nerve stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: (1) diagnosed with idiopathic PD according to the Movement Disorder Society Clinical Diagnostic Criteria for PD; (2) meeting Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for anxiety and Hamilton Anxiety Scale (HAMA) score ≥ 12; (3) stable pharmacotherapy for PD at least one month prior to the study; (4) 40-80 years old; (5) willing to sign written informed consent. Exclusion Criteria: (1) with cognitive impairment, according to Montreal Cognitive Assessment (MOCA) < 23; (2) took antianxiety drugs; (3) with taVNS contraindications; (4) received VNS treatment during the past month; (5) with concomitant severe neurologic, renal, cardiovascular, or hepatic disease.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active Transcutaneous auricular vagus nerve stimulation<br>Two modiﬁed dot-like electrodes delivered the stimulation 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; 20 Hz lasting 7 seconds, alternated with 4 Hz lasting 3 seconds，repeat until 30 min. Every PD patient received stimulation twice daily , 30 minutes each time, for 14 consecutive days. The stimulation intensity was set as the maximum value the patient could tolerate without causing pain. | Device: Active Transcutaneous auricular vagus nerve stimulation<br>* Two modiﬁed dot-like electrodes delivered the stimulation 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; 20 Hz lasting 7 seconds, alternated with 4 Hz lasting 3 seconds，repeat until 30 min. Every PD patient received stimulation twice daily , 30 minutes each time, for 14 consecutive days. The stimulation intensity was set as the maximum value the patient could tolerate without causing pain.<br>|
| Sham Comparator: Sham Transcutaneous auricular vagus nerve stimulation<br>Two modiﬁed dot-like electrodes delivered the stimulation to the left earlobe. Stimulation parameters: frequency = 20/4 Hz; pulse width = 200 μs; 20 Hz lasting 7 seconds, alternated with 4 Hz lasting 3 seconds，repeat until 30 min. Every PD patient received stimulation twice daily , 30 minutes each time, for 14 consecutive days. The stimulation intensity was set as the maximum value the patient could tolerate without causing pain. | Device: Sham Transcutaneous auricular vagus nerve stimulation<br>* Two modiﬁed dot-like electrodes delivered the stimulation 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; 20 Hz lasting 7 seconds, alternated with 4 Hz lasting 3 seconds，repeat until 30 min. Every PD patient received stimulation twice daily , 30 minutes each time, for 14 consecutive days. The stimulation intensity was set as the maximum value the patient could tolerate without causing pain.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change of Hamilton Anxiety Scale Score | Hamilton Anxiety Scale (HAM-A score), which was used for assessing the degree of anxiety. It consists of 14 symptomatic definition elements, with a total possible score of 56. The differences in HAMA score before and after treatment can be used to evaluate the effect of taVNS treatment. | Assessed at baseline, one day post intervention，2 weeks post intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change of HbO2 in the prefrontal cortex | The change of HbO2 in the prefrontal cortex is accessed by fNIRS combined with verbal fluency task. Recent documents have highlighted the effectiveness of fNIRS combined with verbal fluency task (VFT) in detecting alterations in the PFC in patients with anxiety. The differences in HbO2 before and after treatment can be used to evaluate the effect of taVNS treatment. | Assessed at baseline, one day post intervention | 
| change of Uniﬁed Parkinson's Disease Rating Scale Score section III | Uniﬁed Parkinson's Disease Rating Scale Score section III were used to assess the severity of motor symptoms. | Assessed at baseline, one day post intervention，2 weeks post intervention | 
| change of Uniﬁed Parkinson's Disease Rating Scale Score section I | Uniﬁed Parkinson's Disease Rating Scale Score section I can evaluate changes in mental state and cognition (including behavior and emotions) | Assessed at baseline, one day post intervention，2 weeks post intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Parkinson's disease, Anxiety, taVNS