Blinding and Adverse Effects of Ultrasonic Vagus Nerve Stimulation (U-VNS) in Tinnitus (BLAST II)

University of Nottingham

Status: Completed

Conditions: Tinnitus

Treatments: Device: Device: Ultrasound Vagus Nerve Stimulation (U-VNS); Device: Sham Comparator: Sham

Study type: Interventional

Funder types: Other

Identifiers

NCT07291648

FMHS 183-0625

Details and patient eligibility

About

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).

A study found that healthy volunteers can't tell whether they're receiving real U-VNS or sham. It also found that adverse effects are mild, short-lasting and are most commonly feelings of pressure, pain, tingling or warming up of the skin where the device sits on the ear. The next step is to see whether these findings are the same in people with tinnitus. This study aims to 1) investigate the effectiveness of blinding of U-VNS vs sham, 2) evaluate the intensity, onset and duration of any adverse effects of U-VNS in people with tinnitus, and 3) assess the acceptability of U-VNS in people with tinnitus.

Enrollment: 20 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Aged 18 years or over
• Has experienced constant idiopathic tinnitus for at least 6 months
• Participant is willing and able to give informed consent for participation in the study
• Not currently taking any medication (except the contraceptive pill)
• Able and willing to remove any piercings in the left ear

Exclusion criteria

• Current or past diagnosis of a neurological or psychiatric condition
• Current or past diagnosis of cardiac arrhythmia
• No tinnitus
• Has tinnitus, but it is objective, intermittent or onset is less than 6 months ago
• 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)
• Having taken part in a research study in the last 3 months involving invasive procedures or an inconvenience allowance (this must remain for ALL UoN FMHS UREC approved studies)

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Single Blind

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20 participants in 2 patient groups, including a placebo group

Device: Ultrasound Vagus Nerve Stimulation (U-VNS)

Experimental group

Description:

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).

Treatment:

Device: Sham Comparator: Sham

Device: Device: Ultrasound Vagus Nerve Stimulation (U-VNS)

Device: Sham U-VNS

Placebo Comparator group

Description:

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.

Treatment:

Device: Sham Comparator: Sham

Device: Device: Ultrasound Vagus Nerve Stimulation (U-VNS)