Blinding and Adverse Effects of Ultrasonic Vagus Nerve Stimulation (U-VNS)

Not Applicable

Completed

• Conditions: U-VNS; Sham U-VNS

• Registration Number: NCT07091812
• Lead Sponsor: University of Nottingham

Brief Summary

The vagus nerve is a large nerve that runs from the gut to the brain. It consists of two main sections, left and right, and comprises a series of branches. One of these branches runs through the ear. Stimulating the vagus nerve with a stimulation device, either implanted in the body or applied to the skin, has been used to treat a number of health conditions associated with the functioning of the vagus nerve. It has also been explored for tinnitus. Tinnitus is the perception of sound in the absence of an external source. It is believed to be related to abnormal activity in the brain. Stimulation of the vagus nerve may be an effective way of normalising this brain activity, thereby reducing tinnitus.

Two types of vagus nerve stimulation (VNS) have been trialled: 1) invasive VNS, using a surgically implanted vagus nerve stimulator and 2) non-invasive VNS, using electrical stimulation devices that are placed on the skin, near a section of the vagus nerve. Past studies of these techniques show that VNS may be a promising future treatment for tinnitus. However, there is not enough data available to draw a firm conclusion on whether VNS is effective at reducing tinnitus or not. Furthermore, all previous studies of VNS for tinnitus have used electrical stimulation of the vagus nerve. Stimulating the vagus nerve, whether through an implanted device or a device on the skin, comes with serious technical challenges. Most importantly, electric currents follow the path of least resistance. When running through biological tissues, such as skin, cartilage or bone, it is difficult to aim for the part of the body that needs to be stimulated. This means it isn't always easy to tell whether the vagus nerve is indeed being stimulated and how much of the current is actually reaching the vagus nerve.

This problem can be overcome by ultrasound stimulation. Ultrasound stimulation employs high frequency sound waves to stimulate tissue. These soundwaves travel through the human body much more predictably than electric currents. As such, ultrasound stimulation of the vagus nerve may be more effective than electrical stimulation. The ZenBud device is designed to apply ultrasound stimulation to part of the vagus nerve that runs through the ear. Ultrasound stimulation allows for more targeted stimulation, increasing the chance of the stimulation reaching the vagus nerve. The ZenBud device is safe for use in healthy adults and received CE marking based on CE assessments conducted at the University of Nottingham Appendix VI-IX).

However, before this device can be used to test whether this approach can reduce tinnitus symptoms, two questions must be answered: Firstly, can people tell whether they're receiving the real VNS or a placebo? Secondly, what are the type, onset and duration of any adverse effects resulting from U-VNS? We know from the testing performed as part of the CE marking that it is safe. However, there may still be mild adverse effects, such as redness, warming up of the skin etc. It is important to understand these mild adverse effects, so that participants can be fully informed.

Detailed Description

Not available

Study Timeline

• Study Start: 2024-12-10
• Primary Completion: 2025-02-28
• Study Completion: 2025-06-28
• Status Verified: 2025-07
• Study First Submitted: 2025-07-11
• Study First Submitted QC: 2025-07-24
• Last Update Submitted: 2025-07-24
• Study First Posted: 2025-07-29
• Last Update Posted: 2025-07-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

• Aged 18 or over
• Good general health
• Willing and able to provide informed consent
• Not currently taking any prescribed medication (except contraceptive pill)
• Able and willing to remove any piercings in the ears

Exclusion Criteria

• Current or past diagnosis of a neurological psychiatric condition
• Current or past diagnosis of cardiac arrhythmia
• Use of medication or recreational drugs that affect the nervous system in the past 3 months
• Currently pregnant
• Allergy to aquasonic gel or any of its components (propylene glycol, glycerin, isothiazolinones)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Primary Outcome Measures

Name	Time	Method
Effectiveness of blinding and adverse effects questionnaire	Day 1, post-intervention and Day 8, post-intervention	Questionnaire to assess effectiveness of blinding and characterise adverse effects. Question relating to blinding: participants were asked "Do you believe you received real or sham stimulation?" and given the options Real, Sham, and I don't know to choose from. The responses were used to calculate James' Blinding Index. Adverse effects: participants were asked at the end of each session: "Please indicate the extent to which, if any, you felt the following sensations by using the scale below" followed by a list of possible effects: Itching, Burning, Pain, Tingling, Headache, Warmth/heat, Metallic taste, Fatigue, Nausea, Redness, Other and the rating options None, Mild, Moderate and Severe. Participants were also asked "How long did the sensations last?" with the options It stopped quickly, It stopped around the middle of the session, It stopped around the end of the session and It continued after the end of the session.

Trial Locations

Locations (1)

NIHR Nottingham BRC Hearing Theme; 🇬🇧 Nottingham, United Kingdom