Auricular Vagus Nerve Stimulation for Anxiety and Sleep Quality in Patients With Generalized Anxiety Disorder
Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) Effect on Anxiety Severity and Sleep Quality in Patients With Generalized Anxiety Disorder (GAD) in Birjand, Iran in 2026 - Randomized, Double-blind, Sham-controlled Feasibility Trial
The goal of this feasibility clinical trial is to learn whether a small device that stimulates a nerve in the outer ear can be safely and practically used at home by adults with generalized anxiety disorder (GAD). The study will also explore whether this treatment may help lower anxiety and improve sleep quality. Participants will be adults aged 18 to 65 years in Birjand, Iran.
The main questions it aims to answer are:
- Is ear stimulation safe and practical for participants to use at home for four weeks?
- Do participants who receive active stimulation have lower anxiety levels than those who receive sham stimulation?
- Does the treatment help improve sleep quality and other anxiety-related symptoms?
- Can participants follow the treatment schedule and use the monitoring devices as instructed?
Researchers will compare active stimulation with sham stimulation. Sham stimulation is a comparison procedure designed to resemble the active treatment but does not deliver the same active stimulation. This comparison will help researchers explore possible treatment effects and assess whether a larger study is practical.
Participants will:
- Complete screening assessments and questionnaires about anxiety, sleep, and other symptoms.
- Be randomly assigned to receive active ear stimulation or sham stimulation.
- Use their assigned device at home for four weeks, following the study instructions.
- Wear a wristband to help record treatment use and selected body measurements.
- Complete assessments during weeks 2 and 4, followed by check-ups during weeks 6 and 8.
- Report any side effects and provide information about their experience using the device.
Study Overview
Status
Conditions
Study Type
Enrollment (Estimated)
Phase
- Not Applicable
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Age between 18 and 65 years.
- Confirmed diagnosis of Generalized Anxiety Disorder (GAD) according to DSM-5-TR and ICD-11 criteria (6B00), established through a structured clinical interview conducted by a trained clinician.
- GAD must be the primary psychiatric diagnosis.
- Persistent and excessive worry occurring on most days for at least six months, accompanied by associated symptoms consistent with GAD diagnostic criteria.
- Baseline Hamilton Anxiety Rating Scale (HAM-A) total score of at least 7.
- Generalized Anxiety Disorder 7-item scale (GAD-7) score between 5 and 14.
- Perceived Stress Scale-10 (PSS-10) score of 15 or higher.
- Patient Health Questionnaire-9 (PHQ-9) score of 14 or lower.
- PTSD Checklist for DSM-5 (PCL-5) score below 33.
- Pittsburgh Sleep Quality Index (PSQI) score below 15.
- Beck Depression Inventory-II (BDI-II) score between 0 and 28.
- Participants must be either treatment-free or receiving stable pharmacological treatment for at least six weeks before enrollment.
- Participants receiving pharmacological treatment must agree to maintain their current medication regimen throughout the intervention period.
Exclusion Criteria:
- Diagnosis of post-traumatic stress disorder (PTSD), complex PTSD, social anxiety disorder, panic disorder, or specific phobia as a primary diagnosis.
- Moderate-to-severe depressive symptoms, defined as a PHQ-9 score of 15 or higher.
- Diagnosis of bipolar disorder or psychotic disorders.
- Active suicidal ideation requiring immediate clinical intervention.
- Substance use disorder within the six months preceding enrollment.
- Current use of other neuromodulation therapies.
- Presence of implanted electronic medical devices.
- Serious or uncontrolled cardiovascular or neurological conditions.
- Pregnancy or breastfeeding.
- Participation in another interventional clinical study within 30 days before enrollment.
- Initiation of a new medication or any change in medication dosage within six weeks before enrollment.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Active Comparator: Active
|
Participants assigned to the active intervention group will use a transcutaneous auricular vagus nerve stimulation (taVNS) device at home for four weeks. Stimulation will be administered daily according to the study protocol. Participants will receive instructions on device use and will wear a monitoring wristband to help track adherence and selected physiological measures. Safety, tolerability, usability, and adherence will be assessed during the study. Assessments will take place at weeks 2 and 4, with follow-up at weeks 6 and 8 |
|
Sham Comparator: sham
|
Participants assigned to the sham control group will use the taVNS device at home for four weeks, following the study protocol. Stimulation will be delivered at the same site as in the active intervention group, but at a current intensity below 0.1 mA, as specified in the protocol. This sham procedure is intended to provide a comparison condition while helping maintain participant blinding. Participants will receive instructions on device use, and adherence, safety, and tolerability will be assessed during the study. Assessments will take place at weeks 2 and 4, with follow-up at weeks 6 and 8. |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Change in Anxiety Severity Measured by the Hamilton Anxiety Rating Scale (HAM-A)
Time Frame: Baseline to Week 8
|
Anxiety severity will be assessed using the Hamilton Anxiety Rating Scale (HAM-A), a 14-item clinician-administered scale designed to evaluate the severity of anxiety symptoms. Each item is scored from 0 (not present) to 4 (very severe), yielding a total score ranging from 0 to 56, with higher scores indicating greater anxiety severity. The change in total HAM-A score from baseline to Week 8 will be calculated and compared between the active taVNS and sham stimulation groups. A greater reduction in score indicates a greater improvement in anxiety severity. |
Baseline to Week 8
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Change in Sleep Quality Measured by the Pittsburgh Sleep Quality Index (PSQI)
Time Frame: Baseline to Week 8
|
Sleep quality will be assessed using the Pittsburgh Sleep Quality Index (PSQI), a validated self-reported questionnaire consisting of 19 items that evaluate sleep quality and disturbances over the previous month. The questionnaire generates seven component scores, which are summed to produce a global score ranging from 0 to 21. Higher scores indicate poorer sleep quality. The change in the global PSQI score from baseline to Week 8 will be calculated and compared between the active taVNS and sham stimulation groups. A greater reduction in score indicates an improvement in sleep quality. |
Baseline to Week 8
|
|
Incidence of Adverse Events During the Intervention Period
Time Frame: Baseline through Week 8
|
The safety and tolerability of transcutaneous auricular vagus nerve stimulation (taVNS) will be evaluated by monitoring adverse events throughout the intervention period. The number and proportion of participants experiencing at least one adverse event will be recorded in each study group. All reported adverse events will be documented, including their type, severity, duration, and potential relationship to the assigned stimulation intervention. |
Baseline through Week 8
|
|
Adherence to the Assigned Stimulation Protocol
Time Frame: 4 weeks
|
Adherence to the assigned stimulation protocol will be assessed based on the proportion of prescribed stimulation sessions successfully completed by each participant during the 4-week intervention period. The number of completed sessions will be recorded and compared with the total number of prescribed sessions. Adherence will be expressed as a percentage, calculated as the number of completed sessions divided by the total number of prescribed sessions, multiplied by 100. Higher percentages indicate better adherence to the intervention protocol. |
4 weeks
|
|
Success of participant blinding to treatment allocation in the active and sham stimulation groups
Time Frame: at week 4 (end of intervention)
|
The success of participant blinding will be evaluated at the end of the intervention period. Participants will be asked to indicate whether they believe they received active taVNS or sham stimulation. The proportion of participants in each group who correctly and incorrectly identify their assigned intervention will be calculated to assess the effectiveness of participant blinding. |
at week 4 (end of intervention)
|
Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 458167
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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