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Trial registered on ANZCTR


Registration number
ACTRN12615000392561
Ethics application status
Approved
Date submitted
14/04/2015
Date registered
28/04/2015
Date last updated
9/03/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Clinical trial of a take-home rehabilitation device for vestibular patients.
Scientific title
Incremental vestibular rehabilitation training in patients with partial peripheral vestibular dysfunction: balance function outcomes compared between current and proposed rehabilitation techniques.
Secondary ID [1] 286532 0
Nil
Universal Trial Number (UTN)
U1111-1168-9612
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Reduced vestibulo-ocular reflex response (due to peripheral vestibular dysfunction only). 294760 0
Condition category
Condition code
Physical Medicine / Rehabilitation 295039 295039 0 0
Physiotherapy
Ear 295040 295040 0 0
Other ear disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
We have designed and built a small, non-invasive, safe, battery-driven, portable, head-mounted programmable device that patients will use to train at home (i.e., with the dosage / compliance recorded). Both control and intervention groups will be asked to perform current best practice rehabilitation, which are home-based exercises 5 times daily for a total of 30-40 min per day, with changes in exercises from week to week. After these exercises, both groups will perform the device or placebo intervention for 15 minutes. Patient's will be asked to perform these exercises for 6 months followed by a 6 month washout period. At the end of the 6 month washout period patients will again be asked to perform exercises with the device, but will change groups, i.e., if they were in the intervention group for the first 6 months they go into the placebo group for the second 6 months and vice versa. The second 6 months is also followed by a 6 month washout period.

The intervention exercise consists of the patient rapidly turning their head leftwards by a small angle (i.e., a 5-10 degree turn), then slowly returning the head back to neutral, followed by a similarly rapid rotation rightwards. The patient’s task will be to visually track a moving laser dot target on the wall in front of them while they keep turning their head. The basis of incremental adaptation training is that tracking the target starts off easy and gradually gets harder for the patient. This approach has been shown to be more effective at increasing the vestibulo-ocular reflex response compared to tracking a stationary target while turning the head, i.e., a difficult task for vestibular patients. Patients will be educated by one of the researchers listed on our protocol to use the device during their first (baseline) session at our laboratory,

In the test group, subjects will use the rehabilitation device at home for 15 minutes once daily performing the new incremental adaptation technique we developed. In the control group, subjects will also use the rehabilitation device at home for 15 minutes once daily; however, the device will project a stationary visual target, so that the training is identical to one of the exercises performed in current best practice.

A log is automatically maintained on the device to record compliance, whereas patients must manually record their compliance to current best practice via diary. Patients will be asked to bring their diary with them to each monthly visit to our laboratory.
Intervention code [1] 291623 0
Treatment: Devices
Intervention code [2] 291677 0
Rehabilitation
Comparator / control treatment
The rehabilitation device is set in a mode that results in training identical to current best practice.
Control group
Active

Outcomes
Primary outcome [1] 294803 0
Vestibulo-ocular reflex (VOR) gain

Head impulse Test (HIT): A head impulse consists of a manual, passive, unpredictable, head rotation with peak-acceleration 3000deg/s/s. For this test eye movements will be measured using either the scleral search coil or video-oculography technique.
Timepoint [1] 294803 0
Time point: at baseline and once per month for at least 24 months.
Primary outcome [2] 294804 0
Dizziness Handicap Inventory (DHI) Score
Questionnaire: Activities of Daily Living
Timepoint [2] 294804 0
Time point: at baseline and once per month for at least 24 months.
Primary outcome [3] 294805 0
Gait Stability scores

Using an established method (Menz et al., 2003ab), linear accelerations and rotations of the body and head will be measured along three orthogonal axes (vertical, antero-posterior and medio-lateral) using two tri-axial accelerometers and gyroscopes while subjects walk a 30 m path with eyes open and eyes shut. Acceleration levels (RMS), acceleration variability, step timing variability, and harmonic ratio (indicates smoothness and rhythm of body and head) are the key measures of posture and balance control during locomotion. Gait velocity, cadence are included as covariates in these analyses.
Timepoint [3] 294805 0
Time point: at baseline and once per month for at least 24 months.
Secondary outcome [1] 314087 0
Dynamic Visual Acuity (DVA) score

Dynamic Visual Acuity Test (DVAT): The DVAT works on a similar principle to the HIT. Head impulses are delivered to the subject. However, here the subject’s task is to identify the orientation (up, down, left, right) of an optotype (the letter E) presented at different visual acuity levels. The DVAT measures the impact of vestibular hypofunction on visual acuity. An improvement in visual acuity, with no underlying change in vestibular function, would indicate that other oculomotor mechanisms (e.g., the saccadic or smooth pursuit system) are contributing to gaze stabilisation. This improvement could be due to vestibular rehabilitation.
Timepoint [1] 314087 0
Time point: at baseline and once per month for at least 24 months.
Secondary outcome [2] 314090 0
Standing Balance scores

Postural sway and Centre of Pressure excursions will be measured using a CODA motion analysis system integrated with two Kistler force plates. RMS and peak-to-peak in the antero-posterior and lateral directions (markers at pelvis, C7 and head) will be obtained while participants stand for 30 s, each on rigid floor and foam rubber, each with eyes open and shut. These combinations will provide markers of visual, proprioceptive and vestibular contributions to sway stabilisation.
Timepoint [2] 314090 0
Time point: at baseline and once per month for at least 24 months.

Eligibility
Key inclusion criteria
Participants must have a well-defined, isolated, peripheral, vestibular lesion, but are otherwise healthy. These lesions could be due to: Meniere’s disease, vestibular neuritis, labyrinthitis, vestibular neurectomy, semicircular canal plugging, superior canal dehiscence and post-intratympanic gentamicin treatment. Participants can have complete or incomplete unilateral lesions, or incomplete bilateral lesions, i.e., they must have some residual peripheral vestibular function.
Minimum age
18 Years
Maximum age
85 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
People not fluent in English are unsuitable for these studies and will not be recruited.

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)
Patients seen at Royal North Shore Medical Centre (RNSMC) (Dr. Cremer’s private practice), Prince of Wales Private Hospital (POWPH) or Blacktown Neurology (Dr. Watson’s private practices) with a well-defined, isolated, peripheral vestibular lesion, but otherwise healthy, may participate in this study.

Prior to seeing their treating physician (Drs Cremer or Watson) potential patient participants, as determined by the physician support staff, will be handed a flyer with my laboratory contact details. ONLY if the patient initiates a discussion about the study will the treating physician discuss the study with their patient. ONLY if the patient makes first contact with my laboratory will the other personnel listed on our protocol discuss the study with them.

We will offer to email/mail the potential participant a copy of the Participation Information Sheet and Consent Form. Prior to the first laboratory test session one of the personnel listed on our protocol will obtain consent, including: explaining the tests and risks involved, making clear that the participant can withdraw at any time from the study, answer questions, and witness the participant signature.

Participants will be randomly allocated to one of two treatment groups. The person involved in programming the rehabilitation device for each patient will also be responsible for running the group randomization software and maintaining the confidential patient group list. The patient and the researchers recruiting, performing the testing and processing the data will be blinded as to whether the patient is in the control or test group. Thus, allocation involves contacting the holder of the allocation schedule, i.e., the rehabilitation device programmer, who is at the central administration site and does not interact with the participants.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The randomized controlled trial will conform to CONSORT guidelines. We will implement permuted block randomization using software to initially assign patients to one of 2 equal-sized groups: control and test groups.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Phase 2
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Repeated-measures testing of in-between and final test performance for the continuously-scored primary and secondary outcome measures will be made using General Linear Mixed Models (LMM) controlling for pre-rehabilitation performance and other potential confounders. All analyses will be by intention to treat and Bonferroni corrections will be made to adjust for multiple statistical testing. The effect of our rehabilitation technique on each outcome measure will be established using multivariate modelling techniques including multiple linear and logistic regression analyses. This analysis will determine whether our rehabilitation technique will provide significant, objective, short- and long-term benefits to patients.

Power analysis for cross-over design indicates that 16 subjects allows us to detect a 15% VOR response (gain) increase due to vestibular adaptation training (mean1= 0.5, mean2 = 0.575, standard deviation = 0.1, a = 0.05, power = 0.8, 2-sided test). From previous experience we foresee that most patients (~75%) will participate for the duration of study. However, as a contingency for dropout, we will enrol 20 subjects. To fully determine functional changes due to vestibular rehabilitation complete data sets from 20 patients with unilateral and 20 patients with bilateral peripheral vestibular hypofunction will be needed. So we estimate a total of 40 subjects will be required. However, we would like to recruit up to 60 participants in case our 75% continuing participation rate is an underestimation.

Recruitment
Recruitment status
Recruiting
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 in Australia
Recruitment state(s)
NSW
Recruitment postcode(s) [1] 9524 0
2031 - Randwick
Recruitment postcode(s) [2] 9525 0
2148 - Blacktown
Recruitment postcode(s) [3] 9526 0
2065 - St Leonards

Funding & Sponsors
Funding source category [1] 291093 0
Government body
Name [1] 291093 0
National Health and Medical Research Council of Australia (NHMRC)
Address [1] 291093 0
National Health and Medical Research Council
GPO Box 1421
Canberra ACT 2601
Country [1] 291093 0
Australia
Primary sponsor type
Other
Name
Neuroscience Research Australia
Address
139 Barker St,
Randwick, 2031, NSW
Country
Australia
Secondary sponsor category [1] 289770 0
None
Name [1] 289770 0
Address [1] 289770 0
Country [1] 289770 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292674 0
University of New South Wales Human Ethics Committee
Ethics committee address [1] 292674 0
UNSW Research Ethics & Compliance Support
Level 3, Rupert Myers Building (South)
The University of New South Wales
Sydney NSW 2052 Australia
Ethics committee country [1] 292674 0
Australia
Date submitted for ethics approval [1] 292674 0
18/11/2014
Approval date [1] 292674 0
05/05/2015
Ethics approval number [1] 292674 0
HC14319

Summary
Brief summary
A randomized controlled trial will be conducted in 60 people with injury to their balance organ and/or balance nerve. We have developed a safe, non-invasive, ‘incremental’ rehabilitation technique that after a single 15 minute session increases the vestibular (balance) response many times more than current best practice, which takes 6-8 weeks to see any increase. We have shown that the technique can be successfully administered using a small portable device under a controlled setting. This project will determine the long–term (minimum of 24 months) changes in vestibulo-ocular reflex (VOR), balance and gait function in vestibular patients that train once daily (i.e., fixed dosage).
Trial website
Trial related presentations / publications
Peer-reviewed papers:
1. Migliaccio AA, Schubert MC. Pilot study of a new rehabilitation tool: Improved unilateral short-term adaptation of the human angular vestibulo-ocular reflex. Otol. Neurotol. 2014 Dec;35(10): e310-6.
2. Migliaccio AA, Schubert MC. Unilateral adaptation of the human angular vestibulo-ocular reflex. J Assoc Res Otolaryngol. 2013 Feb;14(1):29-36.]

Conference Talks:
1. Migliaccio AA Vestibulo-ocular reflex adaptation and compensation mechanisms. Federation of European Neuroscience Societies (FENS) satelite meeting, Como, Italy 2014. (Invited keynote speaker, all fees waived, July 2014)
2. Migliaccio AA The effect of retinal image error update rate on human vestibulo-ocular reflex gain adaptation. Barany, Buenos Aires, Argentina 2014.(May 2014)
3. Migliaccio AA Functional vestibular rehabilitation using a promising new technique. Sydney Alliance for Healthcare, Research and Teaching (SAHRT), Sydney, Australia 2013 (Invited symposium speaker)
4. Migliaccio AA A new technique to increase the human vestibulo-ocular reflex gain that has potential for vestibular rehabilitation. Neuro-otology society of Australia (NOTSA) conference, Sydney, Australia, 2014. (Invited speaker, all fees waived.)
5. Migliaccio AA Unilateral incremental adaptation of the vestibulo-ocular reflex: A promising method for improving gaze stability after a unilateral vestibular lesion. Neuro-otology society of Australia (NOTSA) conference, Newcastle, Australia 2011.

Conference Posters:
1. C Todd, P Hubner, P Hubner, M Schubert and A Migliaccio (Presenting). Unilateral Incremental Vestibulo-ocular Reflex Adaptation Training in Normal Subjects. Poster at the FENS Satelite Meeting, Como, Italy 2014.
2. C Todd, P Hubner, A Migliaccio (Presenting) and M Schubert. Incremental Vestibulo-ocular Reflex Adaptation Training in Patients with Peripheral Vestibular Hypofunction. Poster at the FENS Satelite Meeting, Como, Italy 2014.
3. C Todd, P Hubner, P Hubner, M Schubert and A Migliaccio. Dynamic Visual Acuity before and after Unilateral Incremental Vestibulo-ocular Reflex Adaptation Training in Normal Subjects. Poster at the Barany Main Meeting, Beunos Aires, Argentina 2014.
4. C Todd, P Hubner, A Migliaccio and M Schubert. Dynamic Visual Acuity before and after Incremental Vestibulo-ocular Reflex Adaptation Training in Patients with Peripheral Vestibular Hypofunction. Poster at the Barany Main Meeting, Beunos Aires, Argentina 2014.
5. AA Migliaccio (presenting) and MC Schubert. Unilateral adaptation of the human angular vestibulo-ocular reflex. Poster at the Association for Research in Otololaryngology Midwinter Meeting, Baltimore, USA 2013.
Public notes

Contacts
Principal investigator
Name 56546 0
A/Prof Americo Migliaccio
Address 56546 0
Balance and Vision Laboratory
Neuroscience Research Australia
139 Barker St
Randwick, 2031, NSW
Country 56546 0
Australia
Phone 56546 0
+61 2 93991030
Fax 56546 0
Email 56546 0
a.migliaccio@neura.edu.au
Contact person for public queries
Name 56547 0
A/Prof Americo Migliaccio
Address 56547 0
Balance and Vision Laboratory
Neuroscience Research Australia
139 Barker St
Randwick, 2031, NSW
Country 56547 0
Australia
Phone 56547 0
+61 2 93991030
Fax 56547 0
Email 56547 0
a.migliaccio@neura.edu.au
Contact person for scientific queries
Name 56548 0
A/Prof Americo Migliaccio
Address 56548 0
Balance and Vision Laboratory
Neuroscience Research Australia
139 Barker St
Randwick, 2031, NSW
Country 56548 0
Australia
Phone 56548 0
+61 2 93991030
Fax 56548 0
Email 56548 0
a.migliaccio@neura.edu.au

No data has been provided for results reporting
Summary results
Not applicable