Treatment of SSD With tcVNS and taVNS

N/AEnrolling By InvitationNCT07198542

National Taiwan University Hospital60 enrolled

Overview

This study aims to compare two non-invasive nerve stimulation devices, gammaCore and Nurosym, to find out which one is more effective in reducing physical discomfort and health-related anxiety in patients with Somatic Symptom Disorder, a condition where individuals experience significant physical symptoms and have excessive thoughts and worries about their health. Participants in this study will receive treatment using both devices at different times. Both devices work by sending mild electrical pulses through the skin to stimulate the vagus nerve, a major nerve that helps regulate body functions. One device (gammaCore) is placed on the neck, while the other (Nurosym) is worn on the ear. The order in which a participant receives the two treatments will be decided by chance, like flipping a coin. Each treatment period will last for two weeks, with a one-week break in between. Over the course of the study (about 8 weeks), participants will visit the hospital for treatment sessions and to complete questionnaires and have non-invasive measurements of body responses, such as heart rate variability.

Official Title: Treatment of Somatic Symptom Disorder with Transcutaneous Cervical Vagus Nerve Stimulation and Transcutaneous Auricular Vagus Nerve Stimulation: A Crossover Randomized Controlled Trial. Study Design: This is a single-center, randomized, single-blind (assessor- and analyst-blinded), crossover clinical trial designed to compare the efficacy of two transcutaneous vagus nerve stimulation (tVNS) devices in patients with Somatic Symptom Disorder (SSD). Participants will be randomly assigned to one of two sequences: (A) Nurosym followed by gammaCore, or (B) gammaCore followed by Nurosym. Each intervention phase consists of 10 daily stimulation sessions administered over a 2-week period (Monday-Friday), followed by a 1-week follow-up assessment. A 1-week washout period will separate the two intervention phases. Primary Objectives: The primary objective is to compare the efficacy of transcutaneous cervical VNS (tcVNS) delivered by the gammaCore device versus transcutaneous auricular VNS (taVNS) delivered by the Nurosym device on the core symptoms of SSD. This will be measured by the change in scores on the Patient Health Questionnaire-15 (PHQ-15) for somatic symptom severity and the Health Anxiety Questionnaire (HAQ) for health anxiety. Secondary Objectives: Secondary objectives include evaluating the effects of both treatments on depression, anxiety, worry, and physiological markers of autonomic nervous system function (e.g., heart rate variability, skin conductance, finger temperature). The study will also explore factors that may predict treatment response. Interventions: Device 1 (gammaCore): Delivers tcVNS. The device will be applied to the neck over the vagus nerve. The daily session involves three 2-minute stimulations on the left side of the neck, followed by three 2-minute stimulations on the right side, for a total daily treatment time of approximately 20 minutes. Device 2 (Nurosym): Delivers taVNS. The device uses an earpiece placed on the left tragus to stimulate the auricular branch of the vagus nerve. The daily treatment consists of one continuous 30-minute session. Stimulation intensity for both devices will be individually titrated for each participant to a level described as a "clear but not uncomfortable or painful sensation". Outcome Measures: Primary Endpoints: The primary endpoints are the change from baseline (Day 1 or Day 29) to the 1-week follow-up assessment (Day 19 or Day 47) in PHQ-15 and HAQ scores for each treatment period . Secondary Endpoints: Secondary outcome measures include the change from baseline to all subsequent assessment points (e.g., Day 5, Day 12, Day 19) in the Beck Depression Inventory-II (BDI-II), Beck Anxiety Inventory (BAI), Penn State Worry Questionnaire (PSWQ), and various physiological parameters. Safety will be assessed by monitoring adverse events throughout the study.

Interventions

gammaCore SapphireDEVICE

This intervention utilizes transcutaneous cervical Vagus Nerve Stimulation (tcVNS). A conductive gel is applied to the device's stimulation surfaces. The device is then placed on the neck over the vagus nerve. The daily treatment protocol consists of three consecutive 2-minute stimulations on the left side of the neck, with a 30-60 second interval between each stimulation. After a brief rest of approximately one minute, the same procedure is repeated on the right side of the neck. The total daily session duration is approximately 20 minutes. Stimulation intensity is individually titrated for each participant to a level that is perceptible but not painful. This regimen is administered once daily for 10 sessions over a 2-week period.

NurosymDEVICE

This intervention utilizes transcutaneous auricular Vagus Nerve Stimulation (taVNS). The device consists of an earpiece electrode that is clipped onto the left tragus. A small amount of water is applied to the skin for conductivity. The daily treatment protocol consists of one continuous 30-minute stimulation session. Stimulation intensity is individually titrated for each participant to a level that is perceptible but not painful. This regimen is administered once daily for 10 sessions over a 2-week period.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Meets the diagnostic criteria for Somatic Symptom Disorder (SSD) according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), as determined by a diagnostic interview with a board-certified psychiatrist. 2. The participant must be receiving stable, routine medical care throughout the trial period. 3. No adjustments to psychiatric or cardiovascular medications for at least one week prior to the start of the study. Exclusion Criteria: 1. Age below 18 or above 65 years. 2. Presence of psychotic symptoms, such as in comorbid schizophrenia. 3. Significant cognitive impairment (e.g., diagnosed dementia or intellectual disability) or difficulty completing the study questionnaires. 4. History of cervical vagotomy. 5. Presence of severe cardiovascular diseases, including: clinically significant tachycardia (resting heart rate \>100 bpm) or bradycardia (resting heart rate \<60 bpm); clinically significant hypertension (systolic \>160 mmHg or diastolic \>100 mmHg) or hypotension (blood pressure \<90/60 mmHg or mean arterial pressure \<65 mmHg); severe coronary artery disease; carotid atherosclerosis or stenosis; aneurysm; congestive heart failure; severe cardiac arrhythmias (e.g., prolonged QT interval, second- or third-degree atrioventricular block, atrial fibrillation, atrial flutter, recent ventricular tachycardia or fibrillation, clinically significant premature ventricular contractions); or myocardial infarction within the last five years. 6. Presence of severe neurological conditions, including severe head trauma, history of epilepsy, brain tumor, or cerebral hemorrhage. 7. Current diagnosis of cancer. 8. Presence of any active implanted medical devices (e.g., cochlear implant, ventricular shunt, implantable vagus nerve stimulator, pacemaker) or non-active implants that may interact with the nervous system (e.g., metal stents, bone plates, screws). 9. Anatomical abnormalities in the neck. 10. Currently pregnant. 11. Wearing jewelry near the tragus that cannot be removed before using the tVNS device. 12. Severe skin disease at the stimulation sites. 13. Known allergy to conductive gel materials. 14. Any other major medical condition that, in the investigator's judgment, could potentially affect the safety or efficacy of vagus nerve stimulation.

Outcomes

Primary Outcomes

Change in Somatic Symptom Severity as Measured by the Patient Health Questionnaire-15 (PHQ-15)

The PHQ-15 is a 15-item self-report scale that assesses the severity of somatic symptoms. Each item is scored from 0 ("not bothered at all") to 2 ("bothered a lot"), resulting in a total score ranging from 0 to 30. Higher scores indicate greater somatic symptom severity. The outcome is the change in the total score from the baseline of each treatment period.

Time frame: Change from baseline (Day 1 for the first period; Day 29 for the second period) to the 1-week post-treatment follow-up assessment (Day 19 for the first period; Day 47 for the second period).

Change in Health Anxiety as Measured by the Health Anxiety Questionnaire (HAQ)

The Health Anxiety Questionnaire (HAQ) is a self-report scale used to measure the severity of health-related anxiety, including worries and beliefs about health. Total scores are calculated, with higher scores indicating a greater level of health anxiety. The outcome is the change in the total score from the baseline of each treatment period.

Secondary Outcomes

Change in Depressive Symptom Severity as Measured by the Beck Depression Inventory-II (BDI-II)

The BDI-II is a 21-item self-report inventory measuring the severity of depression. The total score ranges from 0 to 63, with higher scores indicating more severe depressive symptoms. The outcome is the change in the total score from the baseline of each treatment period.