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Trial registered on ANZCTR


Registration number
ACTRN12613000213741
Ethics application status
Approved
Date submitted
11/02/2013
Date registered
22/02/2013
Date last updated
13/05/2019
Date data sharing statement initially provided
8/04/2019
Date results information initially provided
8/04/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A randomised controlled trial on the efficacy of the selective serotonin re-uptake inhibitor Fluoxetine combined with a computerised multi-sensory training (visual, auditory, tactile) in the treatment of chronic tinnitus in adult sufferers.
Scientific title
A randomised controlled trial on the efficacy of the selective serotonin re-uptake inhibitor Fluoxetine combined with a computerised multi-sensory training (visual, auditory, tactile) in the treatment of chronic tinnitus in adult sufferers.
Secondary ID [1] 281765 0
Nil Known
Universal Trial Number (UTN)
U1111-1138-5235
Trial acronym
MSTS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic tinnitus in adult participants who are otherwise healthy 288080 0
Condition category
Condition code
Ear 288455 288455 0 0
Other ear disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Application of low-dose (20 mg) SSRI (Fluoxetine) via oral administration to promote cortical plasticity 1X/day for 20 days, in conjunction with multi-sensory integration perceptual training (visual, auditory & tactile) also for 20 days, as a novel form of tinnitus treatment. Participants will ingest one 20 mg Fluoxetine tablet daily in the morning and following, engage in the training. The multi-sensory perceptual training will be loaded to a loanable laptop. Following a one hour resting-state MRI session (Centre for Advanced MRI CAMRI) to collect pre-training data and a one hour in-house (University of Auckland labs) session to also collect pre-training tinnitus, hearing and questionnaire-based data: depression, handedness and tinnitus impressions & history, and acclimatize participants to the operation of the laptop and training procedure; participants will engage in the training. They will transport the training to their home environment via the loaned and pre-programmed laptop. Participants will engage in the multi-sensory perceptual training for 30 minutes per day, every day, for 20 days at home. After 20 days, the perceptual training concludes and the participant returns the laptop and engages in post-training, resting-state MRI (CAMRI) and tinnitus & questionnaire assessments (University of Auckland labs).
Intervention code [1] 286308 0
Treatment: Other
Intervention code [2] 286309 0
Rehabilitation
Comparator / control treatment
The treatment will be compared against a placebo in place of the low-dose (20 mg) SSRI (Fluoxetine), administered orally in a pill or tablet form. The placebo will consist of a sugar pill or similar. Depending on the randomised allocation to either the experimental group or the control group, participants will receive either the treatment (SSRI-Fluoxetine) or the placebo once per day for 20 days.
Control group
Placebo

Outcomes
Primary outcome [1] 288618 0
Primary outcome 1: The primary outcome measure will be the Tinnitus Functional Index TFI). A decrease of 13 TFI points or greater, will be indicative of treatment effectiveness.
Timepoint [1] 288618 0
Primary Time point: Baseline, 1 week prior to perceptual training (20 days), immediately post-perceptual training and 3 week's after training cessation (washout).
Secondary outcome [1] 300602 0
Mean Tinnitus Severity Scale score.
Timepoint [1] 300602 0
Primary Time point: Baseline, 1 week prior to perceptual training (20 days), immediately post-perceptual training and 3 week's after training cessation (washout).
Secondary outcome [2] 300603 0
Secondary outcome 2: A reduction in the Tinnitus Handicap Inventory (THI) of 6 points or greater, will be indicative of treatment effectiveness.
Timepoint [2] 300603 0
Primary Time point: Baseline, 1 week prior to perceptual training (20 days), immediately post-perceptual training and 3 week's after training cessation (washout).

Eligibility
Key inclusion criteria
Chronic (> 6 months in duration) tinnitus, that is unilateral (lateralised to one side of the head more than the other), occurring in the adult population (age 18 or older). Less than a 70 dBHL hearing loss in the worse-affected ear for any 1 test frequency. Normal tactile sensitivity as per the Von Frey Monofilament screen. Able to see a computer monitor reliably via a vision check. No musculoskeletal contributors to tinnitus that are outside of scope of a spinal-manual therapist's (a registered chiropractor) treatment practise. No precluding factors to administration of SSRI (Fluoxetine) or resting-state MRI, as indicated by questionnaire and review by specialists in the field of pharmacology and MRI.
Minimum age
18 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1) Hearing loss in the worse-affected ear for any 1 test frequency that is 70 dBHL or greater.
2) Inability to reliably see a computer monitor as per a field-check of vision.
3) Atypical or abnormal tactile sensitivity as indicated by the Von Frey Monofiliment screen.
4) Musculoskeletal contributors to tinnitus that are outside of scope of a spinal-manual therapist's (a registered chiropractor) treatment practise.
5) Precluding factors to administration of low-dose SSRI (Fluoxetine) as indicated by questionnaire and review by specialists in the field of pharmacology.
6) Precluding factors to administration of resting-state MRI as indicated by questionnaire and review by specialists in the field of MRI.

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)
Participants deemed appropriate for candidacy will have their details loaded to a computerised participant counter-balancing programme, which will allocate an alpha-numeric code to each participant for inclusion in the study, thus removing any readily-identifiable information that could be potentially linked to any participant.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants deemed appropriate for candidacy will have their details loaded to a computerised participant counter-balancing programme, which will allocate an alpha-numeric code to each participant for inclusion in the study. Based factors such as: participant's age, gender, handedness, duration of tinnitus and the side the tinnitus is localised to, the programme will randomise and pool participants to either the treatment or placebo groups, and do so in a manner that ensure the groups are well-balanced with regards to the factors listed above.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
A departmental statistician will be engaged to assist with statistical analysis. Statistical analysis will be carried out using IBM SPSS Statistics 19 for Windows (SPSS Inc. an IBM Company, 2010).

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 4789 0
New Zealand
State/province [1] 4789 0
Auckland/Tamaki

Funding & Sponsors
Funding source category [1] 286549 0
University
Name [1] 286549 0
The University of Auckland
Research Faculty

Address [1] 286549 0
The University of Auckland
Research Faculty (Grant Number 3702641)
Private Bag 92019
Auckland CBD, 1142
Country [1] 286549 0
New Zealand
Primary sponsor type
University
Name
The University of Auckland Research Faculty
Address
The University of Auckland
Research Faculty (Grant Number 3702641)
Private Bag 92019
Auckland CBD, 1142
Country
New Zealand
Secondary sponsor category [1] 285489 0
None
Name [1] 285489 0
There is no secondary sponsor - NONE
Address [1] 285489 0
N/A NONE
Country [1] 285489 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 288621 0
New Zealand Health and Disability Ethics Committees (HDEC)
Ethics committee address [1] 288621 0
New Zealand Health and Disability Ethics Committee (HDEC)
Ministry of Health
No 1 The Terrace
PO Box 5013
Wellington, New Zealand



Ethics committee country [1] 288621 0
New Zealand
Date submitted for ethics approval [1] 288621 0
29/01/2013
Approval date [1] 288621 0
12/04/2013
Ethics approval number [1] 288621 0
Ethics committee name [2] 288783 0
The University of Auckland Human Participants Ethics Committee (UAHPEC)
Ethics committee address [2] 288783 0
The University of Auckland
Human Participants Ethics Committee or UAHPEC
(Grant Number 3702641)
Private Bag 92019
Auckland CBD, 1142
Ethics committee country [2] 288783 0
New Zealand
Date submitted for ethics approval [2] 288783 0
12/02/2013
Approval date [2] 288783 0
Ethics approval number [2] 288783 0

Summary
Brief summary
Tinnitus is conscious awareness of sound(s) perceived in the ear(s) and/or the head, occurring without an external, driving sound source and a common symptom of intense sound exposure, ear pathology or hearing loss. Most experience transitory tinnitus and find tinnitus manageable. One in 200 New Zealanders suffer chronic tinnitus and experience life disruption from disturbed: attentional focus, sleep and depression. Brain imaging studies assessing tinnitus have tried to rectify the lack of objective tinnitus measurements. Such studies found tinnitus was linked with regional cortical activation of auditory and non-auditory brain regions indicating networked systems: comprising attention, memory and emotional centres. Hearing-related neuroplastic changes in the auditory pathways and cortex are associated with ear pathology or intense sound exposure, yet findings from tinnitus-related imaging studies suggest brain networks contribute to tinnitus’ perceived severity and pathological sustainability. Recent research has sought to promote cortical plasticity to counteract and treat neuroplastic and network changes associated with tinnitus. Auditory perceptual training using a selective attention format, lead to significant improvements in tinnitus’ effect on daily life and attention. Sensory modality research e.g. vision, hearing and tactile, show modality-specific sensations are either reinforced (heightened) or conflicted with (sensation from one sensory domain is intensified at the expense of another), when paired. No drug therapy for tinnitus currently exists but evidence supports certain Selective Serotonin Reuptake Inhibitors (SSRIs) promote neuroplastic change. Aims: Couple physician-administered, low-dose fluoxetine with integrated, multi-sensory training (visual, auditory, tactile) to promote therapeutic cortical plasticity for treating tinnitus and objectively measure outcomes via resting-state Magnetic Resonance Imaging (MRI).
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 37014 0
Dr Grant Searchfield
Address 37014 0
University of Auckland
Tamaki Innovation Campus
Section of Audiology
Private Bag 92019
Auckland CBD, 1142
Country 37014 0
New Zealand
Phone 37014 0
+64 9 923 6316
Fax 37014 0
Email 37014 0
g.searchfield@auckland.ac.nz
Contact person for public queries
Name 37015 0
Dr Grant Searchfield
Address 37015 0
University of Auckland
Tamaki Innovation Campus
Section of Audiology
Private Bag 92019
Auckland CBD, 1142
Country 37015 0
New Zealand
Phone 37015 0
+64 9 923 6316
Fax 37015 0
Email 37015 0
g.searchfield@auckland.ac.nz
Contact person for scientific queries
Name 37016 0
Dr Grant Searchfield
Address 37016 0
University of Auckland
Tamaki Innovation Campus
Section of Audiology
Private Bag 92019
Auckland CBD, 1142
Country 37016 0
New Zealand
Phone 37016 0
+64 9 923 6316
Fax 37016 0
Email 37016 0
g.searchfield@auckland.ac.nz

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Trial registered before 25th October 2018, ethical approval did not include sharing of data.
What supporting documents are/will be available?
No other documents available
Summary results
Have study results been published in a peer-reviewed journal?
Yes
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary
Multisensory perceptual training resulted in neural connectivity changes consistent with the underlying task. Improvements in tinnitus measures were correlated with changes in sensory and attention networks.