Transcutaneous Vagus Nerve Stimulation for Generalized Anxiety Disorder

Study Overview
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Brief Summary
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This is a randomized, double-blind, parallel-controlled study of patients with generalized anxiety disorder, who will be randomly assigned to either drug-combined transcutaneous vagus nerve stimulation (tVNS) group or drug-combined sham-stimulation group for a period of 4 weeks of treatment.Scale assessments will be performed at baseline, week 1, week 2, week 3, and week 4 of treatment, and brain function monitoring as well as laboratory tests will be performed at baseline and at the end of treatment, respectively.The aim of this study is to investigate the efficacy of medication combined with tVNS and the possible mechanisms of tVNS in the treatment of anxiety.

Official Title
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Efficacy and Mechanism of Transcutaneous Vagus Nerve Stimulation in the Treatment of Generalized Anxiety Disorder

Conditions
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Generalized Anxiety Disorder

Intervention / Treatment
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* Device: medication-combined transcutaneous vagus nerve stimulation
* Device: medication-combined sham stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meeting DSM-5 diagnostic criteria for Generalized Anxiety Disorder; Having a first episode of Generalized Anxiety Disorder or not having used an anxiolytic, antidepressant, antipsychotic, or anticonvulsant medication in the last 1 month. Having a Hamilton Anxiety Scale (HAMA) score of more than 14 and a Hamilton Depression Scale (HAMD-17) score of less than 17. Exclusion Criteria: Having organic brain lesions (e.g., cerebral hemorrhage, massive cerebral infarction, encephalitis, epilepsy); cardiac QTc interval > 450ms; Current or previous diagnosis of other major diseases (e.g., coronary heart disease, pulmonary heart disease, etc.) Currently or previously diagnosed with a mental disorder other than anxiety disorder (except for insomnia disorder); Those who are participating or have participated in vagus nerve stimulation therapy; those who are participating in transcranial magnetic stimulation or transcranial direct current therapy; Pregnant, breastfeeding, or planning to become pregnant during the trial; Refusing to sign the informed consent form.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: medication-combined transcutaneous vagus nerve stimulation group or the medication-combined sham stimulation group
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: medication-combined transcutaneous vagus nerve stimulation<br>Participants will receive anti-anxiety medication and transcutaneous vagus nerve stimulation | Device: medication-combined transcutaneous vagus nerve stimulation<br>* Two electrodes will be applied 2 cm below the left carotid sinus for active stimulation<br>|
| Placebo Comparator: medication-combined sham stimulation group<br>Participants will receive anti-anxiety medication and sham stimulation | Device: medication-combined sham stimulation<br>* Two electrodes will be applied 2 cm below the left carotid sinus for sham stimulation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in the Hamilton Anxiety Scale at Baseline and Week 2 of Treatment | The Hamilton Anxiety Scale is a physician evaluation scale commonly used in clinical practice to assess the level of anxiety in patients. Changes in its scores accurately reflect changes in anxiety symptoms. In this study, changes in scores at baseline and the second week of treatment will be used as the primary outcome measure. | Baseline and Week 2 of the treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in the Hamilton Anxiety Scale at Baseline and Week 4 of Treatment | The Hamilton Anxiety Scale is a physician evaluation scale commonly used in clinical practice to assess the level of anxiety in patients. Changes in its scores accurately reflect changes in anxiety symptoms.Higher scores mean that the patient's anxiety is more severe. | Baseline and Week 4 of the treatment | 
| Changes in the Hamilton Depression Scale at Baseline and Week 2 of Treatment | The Hamilton Depression Scale is a physician evaluation scale commonly used in clinical practice to assess the level of depression in patients. Changes in its scores accurately reflect changes in depressive symptoms.Higher scores mean that the patient is more severely depressed. | Baseline and Week 2 of the treatment | 
| Changes in the Hamilton Depression Scale at Baseline and Week 4 of Treatment | The Hamilton Depression Scale is a physician evaluation scale commonly used in clinical practice to assess the level of depression in patients. Changes in its scores accurately reflect changes in depressive symptoms.Higher scores mean that the patient is more severely depressed. | Baseline and Week 4 of the treatment | 
| Changes in the Generalized Anxiety Scale at Baseline and Week 2 of Treatment | The Generalized Anxiety Scale is a self-assessment scale commonly used in clinical practice to evaluate generalized anxiety symptoms. It has only 7 items and is easy to use.Higher scores mean that the patient's anxiety is more severe. | Baseline and Week 2 of the treatment | 
| Changes in the Generalized Anxiety Scale at Baseline and Week 4 of Treatment | The Generalized Anxiety Scale is a self-assessment scale commonly used in clinical practice to evaluate generalized anxiety symptoms. It has only 7 items and is easy to use.Higher scores mean that the patient's anxiety is more severe. | Baseline and Week 4 of the treatment | 
| Changes in brain function indicators from baseline to end of treatment | Functional near-infrared spectroscopy and event-related potentials will be used in this study to examine brain function in patients.Event-related potential (ERP) is a special brain evoked potential that is generated by intentionally giving a stimulus a special psychological meaning, using multiple or multiple stimuli. Functional near-infrared spectroscopy (fNIRS) can utilize the good scattering of 600-900nm near-infrared light by the main components of blood to obtain changes in oxyhemoglobin and deoxyhemoglobin during brain activity. | Baseline and Week 4 of the treatment | 
| Incidence of adverse events in each group | During the study period, any treatment-related adverse events will be recorded and used to evaluate the safety of the intervention.Common side effects include changes in pronunciation, hoarseness, neck pain, cough, vomiting, etc | Baseline and Week 4 of the treatment |