U-VNSPhase 1/2BLASTNCT07091812
Blinding and Adverse Effects of Ultrasonic Vagus Nerve Stimulation (U-VNS)
A Phase 1/2 study testing Ultrasound Vagus Nerve Stimulation (U-VNS) in people with U-VNS and Sham U-VNS, run by University of Nottingham at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- U-VNS, Sham U-VNS
- What is being tested?
- Ultrasound Vagus Nerve Stimulation (U-VNS)
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 10 Dec 2024to 28 Jun 2025
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
NIHR Nottingham BRC Hearing Theme
Nottingham, NG1 5DU
About this study
Official title: Ultrasonic Vagus Nerve Stimulation: Effectiveness of Blinding and Occurrence of Adverse Effects in Healthy Volunteers
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.
Read more
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
- Being tested
- Ultrasound Vagus Nerve Stimulation (U-VNS), Sham U-VNS
- Keywords
- tinnitus, vagus nerve stimulation, blinding, adverse effects
- Medical subject headings
- Tinnitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ultrasound Vagus Nerve Stimulation (U-VNS)Device
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).
Sham U-VNSDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| U-VNS | Experimental | Active ultrasound vagus nerve stimulation Receives: Device: Ultrasound Vagus Nerve Stimulation (U-VNS) |
| Sham | Sham comparator | Sham device indistinguishable from real U-VNS stimulator Receives: Device: Sham U-VNS |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Day 1, post-intervention and Day 8, post-intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jul 2025
- Study start10 Dec 2024
- Primary completion28 Feb 2025
- Study completion28 Jun 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for U-VNSStudies of the same condition, open and under way.
- More trials run by University of NottinghamThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Nottingham
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Magdalena Sereda, University of Nottingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07091812
- Sponsor's protocol ID
- FMHS 29-1124
- Acronym
- BLAST
- Status last verified
- Jul 2025
- First submitted
- 11 Jul 2025
- Last updated
- 29 Jul 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 29 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ultrasonic Vagus Nerve Stimulation: Effectiveness of Blinding and Occurrence of Adverse Effects in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT07091812
- Acronym / sponsor ID
- BLAST / FMHS 29-1124
- Conditions
- U-VNS, Sham U-VNS
- Keywords
- tinnitus, vagus nerve stimulation, blinding, adverse effects
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- University of NottinghamUniversity, hospital or other
- Study start
- 10 Dec 2024 (actual)
- Primary completion
- 28 Feb 2025 (actual)
- Study completion
- 28 Jun 2025 (actual)
- First posted
- 29 Jul 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| U-VNS | Experimental | Device: Ultrasound Vagus Nerve Stimulation (U-VNS)Active ultrasound vagus nerve stimulation |
| Sham | Sham comparator | Device: Sham U-VNSSham device indistinguishable from real U-VNS stimulator |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (5 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 | U-VNS |
| Sham U-VNSSham 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 | Sham |
Primary outcome
Effectiveness of blinding and adverse effects questionnaire
Time frame: 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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jul 2025.
- Individual participant dataSharing planned: Yes. 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.
Related trials for U-VNS
Recruiting
Non-invasive Ultrasonic Auricular Vagus Nerve Stimulation
Healthy Participants
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Ultrasound Vagus Nerve Stimulation (U-VNS) in people with U-VNS and Sham U-VNS, run by University of Nottingham at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Effectiveness of blinding and adverse effects questionnaire (time frame: Day 1, post-intervention and Day 8, post-intervention). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jul 2025.