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

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.

Conditions

• U-VNS
• Sham U-VNS

Interventions

DEVICE

Ultrasound Vagus Nerve Stimulation (U-VNS)

Ultrasound stimulation of the auricular branch of the vagus nerve using the ZenBud device manufactured by NeurGear (Rochester, New York, USA), a CE-compliant over-the-ear headset. It delivers low-intensity focused ultrasound to the auricular branch of the vagus nerve through several layers of skin (centre frequency 5.3 MHz, pulse repetition rate 41 hertz, 50% duty cycle, average intensity of 1.03 MPa).

DEVICE

Sham U-VNS

Sham device, also produced by NeurGear, which is identical in appearance to the true ZenBud device, emits the same sound and warms up slightly where the transducer sits on the skin.

Sponsors & Collaborators

• University of Nottingham

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

OTHER

Masking

SINGLE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2024-12-10

Primary Completion

2025-02-28

Completion

2025-06-28

Countries

• United Kingdom

Study Locations