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

Ultrasonic Vagus Nerve Stimulation: Effectiveness of Blinding and Occurrence of Adverse Effects in People With Tinnitus

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.

Study Overview

• Status: Completed
• Conditions: Tinnitus
• Intervention / Treatment: Device: Device: Ultrasound Vagus Nerve Stimulation (U-VNS); Device: Sham Comparator: Sham

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Nottingham, United Kingdom
    • University of Nottingham

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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: 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 Comparator: Sham; 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.
Placebo Comparator: 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.	Device: 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 Comparator: Sham; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effectiveness of blinding and adverse effects questionnaire	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.	Day 1 (baseline), immediately post-intervention and Day 8 (follow-up), immediately post-intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tinnitus loudness	Single question: "How strong or loud is your tinnitus right now?" Answer options ranging from 0 (not at all strong or loud) to 10 (extremely strong or loud)	Day 1 (baseline), immediately post-intervention and Day 8 (follow-up), immediately post-intervention

Collaborators and Investigators

• Sponsor: University of Nottingham
• Investigators: Principal Investigator: Bas Labree, PhD, NIHR Nottingham BRC / University of Nottingham

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2025
• Primary Completion (Actual): January 21, 2026
• Study Completion (Actual): January 21, 2026

Study Registration Dates

• First Submitted: November 20, 2025
• First Submitted That Met QC Criteria: December 4, 2025
• First Posted (Actual): December 18, 2025

Study Record Updates

• Last Update Posted (Actual): January 27, 2026
• Last Update Submitted That Met QC Criteria: January 26, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Otorhinolaryngologic Diseases; Sensation Disorders; Ear Diseases; Hearing Disorders; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Tinnitus
• Other Study ID Numbers: FMHS 183-0625

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All data for which consent to share has been obtained will be shared via the University of Nottingham data archive under a CC-BY license. Any data which is deemed to be personally or commercially sensitive will assessed on a case-by-case basis to determine whether it can be shared. There will be no need to update the data past the project period. All published outputs will contain a Data Availability Statement including the datacite DOI that directs to the relevant data set. Data will be released at the same time as any published outputs underpinned by the data or by one year from the end of the project.
• IPD Sharing Time Frame: Data will be released at the same time as any published outputs underpinned by the data or by one year from the end of the project.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No