Condition category
Nervous System Diseases
Date applied
11/10/2019
Date assigned
14/10/2019
Last edited
05/11/2019
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Tinnitus is the perception of a sound in the absence of a sound source. 70% of adults who wear a cochlear implant have tinnitus, with approximately 13% describing tinnitus as a serious concern. It is not fully understood why or how tinnitus occurs, but recently it has been suggested that tinnitus may occur in the process that the brain uses to form perceptions about the world. The brain makes predictions about what is happening in the environment, and for hearing, the default prediction is silence. However, tinnitus can transform into the default prediction instead. There are certain sounds known to change the predictions of the brain (sounds with a certain temporal pattern) which may reduce tinnitus loudness, or even suppress tinnitus.

Who can participate?
Adult cochlear-implant users recruited from the Emmeline Centre for Hearing Implants (Cambridge)

What does the study involve?
We will explore the effect of specially designed sounds in adult cochlear-implant users recruited from the Emmeline Centre for Hearing Implants (Cambridge). We will also determine whether there are any objective markers of tinnitus in the responses of the brain to sound or in the size of the eye pupil during a listening activity (which is a measure of listening effort). Objective markers of tinnitus would be helpful to understand why and how tinnitus occurs. We will compare brain responses to sound across two groups of adult cochlear-implant users, one with tinnitus and another one without tinnitus (Part A) and we will measure the effect of using special sounds (sound textures) on the reduction of tinnitus loudness/annoyance and on the brain responses (Part B). We will also explore the relationship between tinnitus and listening effort.

What are the possible benefits and risks of participating?
Identified benefits: In general, taking part in research can help participants to better understand their condition. No specific benefits were identified for Part A, but participants in Part B could find that one or more sounds used in the study help them to relieve tinnitus.
Identified risks: In general, participants may get tired if sessions are long. Breaks and refreshments have been included in planning in order to reduce this burden as much as possible.
For participants in Part A, focusing on tinnitus in order to reply to the questionnaires could make the volunteer more aware of their tinnitus. This means that their tinnitus may appear louder or they may notice it more frequently. This effect does not occur for most people, and when it does, it is usually temporary.
Additionally, sounds used to relieve tinnitus can sometimes increase tinnitus loudness, but this is more frequent when sounds are loud (as similarly, it is common for tinnitus to be worse after being in noisy places). We will check with the participant the loudness level of any sounds presented to them to make sure that no loud/uncomfortable sounds are presented during the study. Participants will be made aware that they can ask us to interrupt what we are doing any time if they feel uncomfortable.

Where is the study run from?
Cambridge University Hospitals NHS Foundation Trust, UK

When is the study starting and how long is it expected to run for?
November 2019 to June 2020

Who is funding the study?
Addenbrooke's Charitable Trust, Cambridge University Hospitals NHS Foundation Trust, UK

Who is the main contact?
Dr Marina Salorio-Corbetto
ms878@cam.ac.uk

Trial website

Contact information

Type

Scientific

Primary contact

Dr Marina Salorio-Corbetto

ORCID ID

http://orcid.org/0000-0002-5621-5284

Contact details

University of Cambridge
Department of Clinical Neurosciences
Herchel Smith Building for Brain and Mind Sciences
Robinson Way
Cambridge
CB2 0SZ
United Kingdom
+44 (0)7832979916
ms878@cam.ac.uk

Type

Public

Additional contact

Dr Marina Salorio-Corbetto

ORCID ID

Contact details

University of Cambridge
Department of Clinical Neuroscience
Herchel Smith Building for Brain and Mind Sciences
Robinson Way
Cambridge
CB2 0SZ
United Kingdom
+44 (0)1223746454
ms878@cam.ac.uk

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

IRAS Project ID 265044

Study information

Scientific title

Functional impact of tinnitus in post-lingual users of cochlear implants and short-term effects of sound therapy

Acronym

Study hypothesis

Main question: In cases of moderate or severe tinnitus, do 'sound textures' reduce tinnitus loudness/annoyance for adult cochlear-implant users?
Secondary questions:
1. Are there any differences in the electrophysiological or pupillometry findings between the tinnitus group and the no-tinnitus group? This will be addressed in Part A. If found, these can be used as objective markers of tinnitus
2. What are the functional impact and characteristics of tinnitus are in adult users of cochlear implants? This is a secondary question that will be addressed in Part A
3. In cases of moderate or severe tinnitus (Part B):
3.1. Do the auditory evoked responses and/or the pupillary responses change after stimulation with sound textures compared to white noise filtered to match their long-term spectrum?
3.2. Are any changes in the objective measures (evoked potentials and electrophysiology) correlated with the reduction of tinnitus loudness/annoyance?

Ethics approval

Approval pending, NHS East of England - Cambridgeshire and Hertfordshire Research Ethics Committee (Level 3, Block B, Whitefriars, Lewins Mead, Bristol, BS1 2NT; +44 (0)207 1048106; nrescommittee.eastofengland-cambsandherts@nhs.net)

Study design

Cross-over randomised-controlled study

Primary study design

Interventional

Secondary study design

Randomised cross over trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

See additional files

Condition

Tinnitus

Intervention

While Part A of the study seeks to explore objective measures of tinnitus, Part B seeks to assess the effect of sound therapy on tinnitus.

In Part B, participants will be asked to come to the research centre for two sessions, each lasting between 2 h 15 min and 2 h 45 min. Breaks will be spaced as needed during the session and tea and refreshments will be provided. If any of the event-related auditory evoked potentials used in Part A is significantly different across participants with and without tinnitus, the type of evoked potential with the highest sensibility and specificity will be used in Part B.

Responses will be obtained at the start of the session. Next, the participant will be presented with a five-minute duration sound texture or with a control sound, randomly chosen. During the presentation of the sound, participants will be prompted to rate the loudness and annoyance of their tinnitus several times (once per minute) using a computer interface. At the end of the stimulation, the evoked potentials will be repeated.

As this is a controlled trial, each participant gets exposed to two sounds, in random order. Therefore, after the first sound was presented, the participant comes back for a second session with the same structure, where the second sound (the sound not presented in the first part of the session) is presented

Intervention type

Other

Phase

Drug names

Primary outcome measure

Part A:
1. Mismatch negativity: Variables are amplitude, latency, and area under the curve
2. Auditory Steady State Response and N1-P2 responses: The variable is amplitude in each case.
3. P300: The variables are amplitude and latency
For all of these outcome measures (1, 2, and 3), the method of measurement is recording event-related auditory evoked potentials
4. Pupillometry: The variable is Pupillar diameter. The method of measurement is pupillometry

Part B:
5. Tinnitus loudness ratings. Methods: Subjective ratings in a visual-analogue scale
6. Tinnitus annoyance ratings. Methods: Subjective ratings in a visual-analogue scale
7. One objective measure selected based on the outcomes of Part A. It could be 1, 2, 3, or 4. The measure with the highest sensitivity to separate between participants with tinnitus and without tinnitus will be used

Secondary outcome measures

Part A:
1. Variable: Tinnitus Functional Index; Method: validated questionnaire
2. Variable: Qualitative data describing each participant's tinnitus. Method: Tinnitus Cochlear Implant Questionnaire, non validated questionnaire
3. Variable: Tinnitus Loudness Ratings; Methods: Subjective ratings in a visual-analogue scale

Overall trial start date

29/10/2019

Overall trial end date

30/06/2020

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

Part A:
1. Adult (aged 18+ years, with no upper limit)
2. Users of unilateral cochlear implants
3. Fluent in English
4. Attend the Emmeline Centre for Auditory Implants
5. Had their cochlear implants switched on for at least one year

Part B:
1. Adult (aged 18+ years)
2. Users of unilateral cochlear implants
3. Attend the Emmeline Centre for Auditory Implants
4. Had their cochlear implants switched on for at least one year
5. Have tinnitus even when their cochlear implant is switched on
6. Scored 32 or higher in the Tinnitus Functional Index questionnaire

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

60

Participant exclusion criteria

Part A and B:
1. Bilateral cochlear implantation
2. Aged less than 18 years
3. Severe visual impairment
4. Severe mental-health condition
5. Severe general-health condition
6. Currently having medication that affects tinnitus or the recording of evoked potentials

Additionally, for Part B:
7. Currently receiving other treatments for tinnitus apart from tinnitus management therapy

Recruitment start date

01/12/2019

Recruitment end date

31/05/2020

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Cambridge University Hospitals NHS Foundation Trust
Hills Road
Cambridge
CB2 0QQ
United Kingdom

Sponsor information

Organisation

Jointly sponsored by the University of Cambridge and Cambridge University NHS Foundation Trust

Sponsor details

Addenbrooke's Hospital
Hills Road
Cambridge
CB2 0SZ
United Kingdom
01223217418
research@addenbrookes.nhs.uk

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Hospital/treatment centre

Funder name

Addenbrooke's Charitable Trust, Cambridge University Hospitals

Alternative name(s)

Addenbrooke's Charitable Trust, Cambridge University Hospitals NHS Foundation Trust, ACT

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Results and Publications

Publication and dissemination plan

The outcomes of the project will be disseminated in national (UK) and international conferences, and other events, such as presentation to the public in science festivals or Patient Associations. Results will be published in international peer-reviewed journals.

IPD sharing statement:
The datasets generated during and/or analysed during the current study will be stored in a non-publically available repository

Intention to publish date

01/01/2021

Participant level data

Stored in repository

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

05/11/2019: The following changes were made to the trial record: 1. The recruitment start date was changed from 01/11/2019 to 01/12/2019. 2. The ethics approval was changed from "NHS HRA REC East of England - Cambridge South" to "NHS East of England - Cambridgeshire and Hertfordshire Research Ethics Committee". 14/10/2019: Trial’s existence confirmed by University of Cambridge