Treatment of SSD With tcVNS and taVNS

NCT07198542 | Enrolling By Invitation

• 1 other identifier: 202411116DIND
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Somatic Symptom Disorder; Anxiety; Depression; Transcutaneous Vagus Nerve Stimulation; Neuromodulation

Keywords

Somatic Symptom Disorder; Transcutaneous Vagus Nerve Stimulation; Neuromodulation; Anxiety; Depression

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  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).

Secondary Outcomes (7)

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

  Change from baseline (Day 1 or Day 29) to each subsequent assessment point (Day 5, Day 12, Day 19 for the first period; Day 33, Day 40, Day 47 for the second period).

• Change in Anxiety Symptom Severity as Measured by the Beck Anxiety Inventory (BAI)

  Change from baseline (Day 1 or Day 29) to each subsequent assessment point (Day 5, Day 12, Day 19 for the first period; Day 33, Day 40, Day 47 for the second period).

• Change in General Worry as Measured by the Penn State Worry Questionnaire (PSWQ)

  Change from baseline (Day 1 or Day 29) to each subsequent assessment point (Day 5, Day 12, Day 19 for the first period; Day 33, Day 40, Day 47 for the second period).

• Change in Autonomic Nervous System Function as Measured by Heart Rate Variability (HRV)

  Change from baseline (Day 1 or Day 29) to each subsequent assessment point (Day 5, Day 12, Day 19 for the first period; Day 33, Day 40, Day 47 for the second period).

• Change in Cardiac Vagal Control as Measured by Respiratory Sinus Arrhythmia (RSA)

  Change from baseline (Day 1 or Day 29) to each subsequent assessment point (Day 5, Day 12, Day 19 for the first period; Day 33, Day 40, Day 47 for the second period).

Study Arms (2)

Group A: gammaCore then Nurosym

EXPERIMENTAL

Participants assigned to this sequence will first receive active transcutaneous cervical vagus nerve stimulation (tcVNS) using the gammaCore device. This initial treatment period consists of 10 daily sessions (approx. 20 minutes each) over 2 weeks, followed by a 1-week follow-up assessment. After a 1-week washout period, participants will cross over to the second treatment period. In this period, they will receive active transcutaneous auricular vagus nerve stimulation (taVNS) using the Nurosym device for 10 daily 30-minute sessions over 2 weeks, followed by a final 1-week follow-up assessment.

Device: gammaCore Sapphire; Device: Nurosym

Group B: Nurosym then gammaCore

EXPERIMENTAL

Participants assigned to this sequence will first receive active transcutaneous auricular vagus nerve stimulation (taVNS) using the Nurosym device. This initial treatment period consists of 10 daily 30-minute sessions over 2 weeks, followed by a 1-week follow-up assessment. After a 1-week washout period, participants will cross over to the second treatment period. In this period, they will receive active transcutaneous cervical vagus nerve stimulation (tcVNS) using the gammaCore device for 10 daily sessions (approx. 20 minutes each) over 2 weeks, followed by a final 1-week follow-up assessment.

Device: gammaCore Sapphire; Device: Nurosym

Interventions

gammaCore Sapphire DEVICE

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.

Also known as: Transcutaneous cervical Vagus Nerve Stimulation, tcVNS

Group A: gammaCore then Nurosym; Group B: Nurosym then gammaCore

Nurosym DEVICE

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.

Also known as: Transcutaneous auricular Vagus Nerve Stimulation, taVNS

Group A: gammaCore then Nurosym; Group B: Nurosym then gammaCore

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• The participant must be receiving stable, routine medical care throughout the trial period.
• No adjustments to psychiatric or cardiovascular medications for at least one week prior to the start of the study.

You may not qualify if:

• Age below 18 or above 65 years.
• Presence of psychotic symptoms, such as in comorbid schizophrenia.
• Significant cognitive impairment (e.g., diagnosed dementia or intellectual disability) or difficulty completing the study questionnaires.
• History of cervical vagotomy.
• 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.
• Presence of severe neurological conditions, including severe head trauma, history of epilepsy, brain tumor, or cerebral hemorrhage.
• Current diagnosis of cancer.
• 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).
• Anatomical abnormalities in the neck.
• Currently pregnant.
• Wearing jewelry near the tragus that cannot be removed before using the tVNS device.
• Severe skin disease at the stimulation sites.
• Known allergy to conductive gel materials.
• Any other major medical condition that, in the investigator's judgment, could potentially affect the safety or efficacy of vagus nerve stimulation.

Sponsors & Collaborators

• National Taiwan University Hospital: lead
• Industrial Technology Research Institute, Taiwan: collaborator

Study Sites (1)

Department of Psychiatry, National Taiwan University Hospital Yunlin Branch

Douliu, Yunlin, 640, Taiwan

Location

MeSH Terms

Conditions

Anxiety Disorders; Depression

Condition Hierarchy (Ancestors)

Mental Disorders; Behavioral Symptoms; Behavior

Study Officials

• Chia-Hao Ma, MD

  Department of Psychiatry, National Taiwan University Hospital Yunlin Branch

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: This is a single-blind study. In addition to the Outcomes Assessor, the Statistical Analyst will also be blinded to the treatment allocation. The analyst will receive a dataset with treatment groups coded (e.g., 'Group A', 'Group B') and will perform the statistical analysis without knowledge of which group corresponds to which intervention. The allocation code will be revealed only after the primary analysis is complete and the results have been confirmed.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 21, 2025
• First Posted: September 30, 2025
• Study Start: November 17, 2025
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: December 12, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)