Trial Review

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12625000152426
Ethics application status
Approved
Date submitted
28/01/2025
Date registered
10/02/2025
Date last updated
10/02/2025
Date data sharing statement initially provided
10/02/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
Vagus nerve stimulation for tinnitus
Scientific title
Paired vagus nerve and auditory stimulation for the treatment of tinnitus: a proof-of-concept and feasibility study
Secondary ID [1] 313824 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Tinnitus 336467 0
Condition category
Condition code
Neurological 332982 332982 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Non-invasive vagus nerve stimulation (VNS) will be applied in conjunction with auditory stimulus. The intervention will be administered three times a week (30 minutes per session) for 3 weeks (9 sessions in total) using the DualSTIM multi-modal stimulator. The three sessions will not occur on three consecutive days; however, two days in a row will be allowed depending on the participants' schedules. Participants will fill out dated surveys when arriving for each session so session dates and attendance will be recorded.

The DualSTIM will electrically stimulate the auricular branch of the vagus nerve using small electrodes that clip to the tragus. It also features a headphone port for audio output. The auditory stimulus will be a tone generated to match a participant's tinnitus percept at each first session by a trained research assistant. Future sessions will also be managed by the same research assistant at a quiet room within Dunedin Hospital.

Participants in the treatment groups will receive 1 second of VNS that is paired with 3 seconds of auditory stimulation (either simultaneously or with a 5 second delay). This will occur repeatedly every 15-20 seconds throughout each 30-minute treatment session. These 15-20 second stimulation periods will have random lengths.
Intervention code [1] 330411 0
Treatment: Devices
Comparator / control treatment
Participants in the control group will receive randomized desynchronized VNS and auditory stimulation. The same 1 second of VNS will occur at the start of each 15-20 second stimulation period. However, the 3 seconds of auditory stimulation will occur at a random time within each stimulation period (so delay could range from 0 to 17 seconds) in order to prevent a strong learning association.
Control group
Active

Outcomes
Primary outcome [1] 340521 0
Recruitment rate
Timepoint [1] 340521 0
End of treatment, end of follow-up stage
Primary outcome [2] 340522 0
Safety
Timepoint [2] 340522 0
Whenever adverse effects occur during the 3-week study period
Primary outcome [3] 340523 0
Tinnitus loudness
Timepoint [3] 340523 0
Before and after each treatment session
Secondary outcome [1] 444330 0
Tinnitus disability
Timepoint [1] 444330 0
Before treatment period, after treatment period, at 1-month follow-up
Secondary outcome [2] 444331 0
Sleep quality
Timepoint [2] 444331 0
Before and after treatment period
Secondary outcome [3] 444332 0
Patient-described treatment efficacy
Timepoint [3] 444332 0
End of each week of treatment (3 times)
At 1-month follow-up
Secondary outcome [4] 444333 0
Depression
Timepoint [4] 444333 0
Before and after treatment period
Secondary outcome [5] 444518 0
Adherence to intervention - this is an additional primary outcome
Timepoint [5] 444518 0
After the 3-week treatment period
Secondary outcome [6] 444519 0
Tinnitus distress - this is an additional primary outcome
Timepoint [6] 444519 0
Before and after each treatment session
Secondary outcome [7] 444520 0
Tinnitus unpleasantness - this is an additional primary outcome
Timepoint [7] 444520 0
Before and after each treatment session
Secondary outcome [8] 444521 0
Drop-out rates - this is an additional primary outcome
Timepoint [8] 444521 0
After the 1-month follow-up phase is completed
Secondary outcome [9] 444522 0
Participant satisfaction levels - this is an additional primary outcome
Timepoint [9] 444522 0
At the 1-month follow-up for each participant
Secondary outcome [10] 444523 0
Anxiety
Timepoint [10] 444523 0
Before and after treatment period
Secondary outcome [11] 444524 0
Stress
Timepoint [11] 444524 0
Before and after treatment period

Eligibility
Key inclusion criteria
Diagnosis of chronic, pure-tone tinnitus
Tinnitus loudness of 4 or higher on a numeric rating scale
Capable of understanding the study information and able to sign the informed consent form
Age above 18 years on the day of the consent
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
History of neurological diseases
History of epilepsy or seizures
Current substance use disorders
Cognitive impairments (dementia, Alzheimer’s disease, personality disorders, substance use disorders, certain medical conditions): a total score of 24 or below on Mini-Mental State Examination
Presence of any pacemaker or defibrillator
Presence of any electronic implants or metal implant in the body (particularly head and neck)

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation created by computer software
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
17/02/2025
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
30
Accrual to date
Final
Recruitment outside Australia
Country [1] 26847 0
New Zealand
State/province [1] 26847 0

Funding & Sponsors
Funding source category [1] 318294 0
University
Name [1] 318294 0
University of Otago
Country [1] 318294 0
New Zealand
Primary sponsor type
University
Name
University of Otago
Address
Country
New Zealand
Secondary sponsor category [1] 320678 0
None
Name [1] 320678 0
Address [1] 320678 0
Country [1] 320678 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 316933 0
Northern B Health and Disability Ethics Committee 
Ethics committee address [1] 316933 0
https://ethics.health.govt.nz/about/northern-b-health-and-disability-ethics-committee/
Ethics committee country [1] 316933 0
New Zealand
Date submitted for ethics approval [1] 316933 0
Approval date [1] 316933 0
22/11/2024
Ethics approval number [1] 316933 0

Summary
Brief summary
Tinnitus is a significant and growing health challenge globally, affecting individuals, their whanau, the wider community, and the healthcare system. Current treatments are ineffective and or are often associated with adverse effects. New innovative safer
therapies are thus warranted. Our study will explore and test the effect of a novel approach pairing vagus nerve stimulation (VNS) and sound stimulation. The VNS has shown to activate the parasympathetic ‘rest-digest-restore’ response. If the sound stimulation is given
immediately after the VNS (i.e., during the parasympathetic activation phase), it would potentially remove the salience attached to an otherwise meaningless tinnitus sound; thus resulting in improved clinical outcomes.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 139470 0
Prof Dirk De Ridder
Address 139470 0
Department of Surgical Sciences, Dunedin School of Medicine, PO Box 56, Dunedin 9054, New Zealand
Country 139470 0
New Zealand
Phone 139470 0
+64275601144
Fax 139470 0
Email 139470 0
[email protected]
Contact person for public queries
Name 139471 0
Dr. Divya Adhia
Address 139471 0
Department of Surgical Sciences, Dunedin School of Medicine, PO Box 56, Dunedin 9054, New Zealand
Country 139471 0
New Zealand
Phone 139471 0
+64211167594
Fax 139471 0
Email 139471 0
[email protected]
Contact person for scientific queries
Name 139472 0
Dr. Divya Adhia
Address 139472 0
Department of Surgical Sciences, Dunedin School of Medicine, PO Box 56, Dunedin 9054, New Zealand
Country 139472 0
New Zealand
Phone 139472 0
+64211167594
Fax 139472 0
Email 139472 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.