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Trial registered on ANZCTR


Registration number
ACTRN12621000139875
Ethics application status
Approved
Date submitted
17/11/2020
Date registered
11/02/2021
Date last updated
14/06/2022
Date data sharing statement initially provided
11/02/2021
Type of registration
Retrospectively registered

Titles & IDs
Public title
A pilot randomised controlled trial of a vestibular-stimulation, isometric exercise machine to manage symptoms of Parkinsonism
Scientific title
A pilot randomised controlled trial of a vestibular-stimulation, isometric exercise machine to manage symptoms of Parkinsonism
Secondary ID [1] 303074 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Parkinson's disease 308705 0
Atypical Parkinsonism 319766 0
Condition category
Condition code
Physical Medicine / Rehabilitation 307644 307644 0 0
Other physical medicine / rehabilitation
Neurological 307648 307648 0 0
Parkinson's disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients randomised to the intervention will undertake two supervised sessions per week on the Reviver exercise machine (http://isodynamics.com.au), each with 15 minutes machine time, for a period of 12 weeks, taking place at the Alfred Hospital, Melbourne. The sessions will be one-on-one.
The machine rotates the body at an angle of 5-30 degrees and subjects must tense their core and peripheral muscles in order to maintain an upright posture. A strap is placed around the patient’s waist to secure them to the machine and prevent falling. This machine design induces isometric exercise via a reflex response to falling, potentially recruiting involuntary muscular activation and deeply ingrained motor programs. The inclined nature of the machine’s motion periodically displaces cochlear fluid and presumably delivers a periodic stimulus to the vestibular nerves.
In each session, patients will undertake 6 exercises on the machine designed by exercise physiologist, which target various aspects of strength and balance:
1) Squatting exercise for leg strength
2) Balancing forward exercise
3) Balancing backward exercise
4) Forward incline exercise, patient supported by straps, for back strength
5) Backward incline exercise, patient supported by straps, for abdominal strength
6) Forward incline exercise, patient supported by own arms, for whole body strength.


The machine will be operated by a trained assistant.
Adherence to the protocol will be recorded as the percentage of sessions attended. Patients will be asked beforehand whether they are willing and able to attend the required number of sessions over the three month period.
Intervention code [1] 301763 0
Treatment: Devices
Intervention code [2] 301764 0
Rehabilitation
Comparator / control treatment
Control subjects will continue their standard of care, with emphasis placed on maintaining their current levels of physical activity. Standard care is defined as maintaining their treatment schedule at baseline. This includes maintaining the same medication dosage and frequency, maintaining the same levels of physical activity , and maintaining any other treatment prescribed by their treating physician at time of enrollment.

At the end of the study, control group participants will be offered the opportunity to undertake a shortened interventional regime on the Reviver machine of 6 x 15 minute sessions over 3 weeks.
Control group
Active

Outcomes
Primary outcome [1] 306634 0
The primary outcome will be the MDS-UPDRS rating scale for Parkinson’s Disease, a set of tests and questionnaires for measuring the severity of the disease. The scale has four sections:
Part I: non-motor experiences of daily living
Part II: motor experiences of daily living
Part III: motor examination
Part IV: motor complications

Parts I, II and IV are questionnaires, delivered orally by the assessor and are rated on a scale of 0-4. Part III requires the patient to perform simple motor tasks, which are observed and assessed by the assessor, and rated on a scale of 0-4.
Timepoint [1] 306634 0
baseline - week prior to commencement of intervention
follow up - 12 weeks after intervention commencement
Secondary outcome [1] 388958 0
Postural Sway
Balance as measured by postural sway, quantified using a digital accelerometer attached to the body and using the CATSYS 2000 force plate platform. Patients will be asked to stand still under two conditions (1) with eyes open fixating on a point (2) with eyes closed. Postural sway will be measured as the root mean squared of acceleration for the anterior-posterior and medio-lateral components of motion measured by the accelerometer, and the root mean squared of accelerations in centre of pressure on the force plate.
Timepoint [1] 388958 0
baseline - week prior to commencement of intervention
follow up - 12 weeks after intervention commencement
Secondary outcome [2] 388976 0
Mobility as measured by electronic tracking of gait on a GAITRite (www.gaitrite.com) pressure sensitive gait mat. Patients will be asked along the gait mat under 3 conditions, (1) regular pace, (2) fast as possible, (3) backwards at comfortable pace. Step length, stride length, gait speed and gait variability index will be calculated.
Timepoint [2] 388976 0
baseline - week prior to commencement of intervention
follow up - 12 weeks after intervention commencement
Secondary outcome [3] 388979 0
Mobility as measured by the timed up and go task. Patients start seated, are required to stand, walk 3 meters, turn around, return 3 meters and sit down. The time from instruction to stand to final seating is recorded.
Timepoint [3] 388979 0
baseline - week prior to commencement of intervention
follow up - 12 weeks after intervention commencement
Secondary outcome [4] 388980 0
Leg strength using the sit to stand test. Patients are timed on how long it takes them to rise from a seated position and sit down again 5 times.
Timepoint [4] 388980 0
baseline - week prior to commencement of intervention
follow up - 12 weeks after intervention commencement
Secondary outcome [5] 388981 0
Quantitative Tremor

Tremor will be measured using a digital accelerometer.
Timepoint [5] 388981 0
baseline - week prior to commencement of intervention
follow up - 12 weeks after intervention commencement
Secondary outcome [6] 390036 0
Vestibular Occular Motor 1): Smooth pursuit:

Enables tracking of objects moving in space. The smooth pursuit system incorporates closed loop neuronal systems that continuously utilises real-time negative feedback, allowing the maintenance of optimal fixation of a target in motion by aligning it with the fovea. Participants are required to fixate a target subtending .5 degree visual angle, and track it as it moves horizontally, back and forth at a constant velocity (250hz). Total task time = 3 minutes. Key measures: accuracy, no. of catchup/backup saccades, anticipatory saccades.
Timepoint [6] 390036 0
baseline - week prior to commencement of intervention
follow up - 12 weeks after intervention commencement
Secondary outcome [7] 390037 0
Vestibular Occular Motor 2) Gaze stability:

Gaze stability occurs via a multi-modal network of vestibular, brain stem, cerebellar, visual and proprioceptive information. Participants are required to maintain fixation of a peripheral target (10 degrees left/right of centre) for 20 seconds. Total task time = 2 minutes. Key measures: latency, maintenance of peripheral gaze hold
Timepoint [7] 390037 0
baseline - week prior to commencement of intervention
follow up - 12 weeks after intervention commencement
Secondary outcome [8] 390038 0
Vestibular Occular Motor 3) Visually guided saccades (horizontal and vertical).

Pseudo-reflexive task of ocular motor control. Assesses integrity of lower level ocular motor areas. Participants follow a target subtending .5 degrees visual angle, as it jumps from left to right (5-10 degrees, left and right), 48 times. Total task time = 2 minutes. Key measures, latency, anticipatory saccades, velocity, main sequence, adaptation of performance over time.
Timepoint [8] 390038 0
baseline - week prior to commencement of intervention
follow up - 12 weeks after intervention commencement
Secondary outcome [9] 390039 0
Vestibular Occular Motor 4) Saccade adaptation:

Since saccades are so fast, usually complete in less than 60 ms or so, there is no time for immediate visual feedback to correct for errors in performance. Hence, the brain must recognize when saccade performance is imperfect and recalibrate premotor commands to restore accuracy. In saccade adaptation paradigms a persistent retinal error is imposed after every primary saccade by jumping the target as soon as the saccade toward the first target began. The first saccade becomes inaccurate requiring a second, corrective saccade to reach the new target location. Within a relatively small number of trials premotor commands gradually change so that the initial saccade grows bigger or smaller (depending upon whether the second target moves farther from or closer to the starting position of the eye). The adapted saccades persist even when training stops and their return to the pre-training state is gradual, not abrupt, suggesting that this is a true form of adaptive plasticity rather than a high-level cognitive strategy. Total task time = 5 minutes. Key measures: latency, final eye position error, time to adaptation, modulation of adaptation over time.
Timepoint [9] 390039 0
baseline - week prior to commencement of intervention
follow up - 12 weeks after intervention commencement
Secondary outcome [10] 390040 0
Vestibular Occular Motor 5) Vestibular ocular reflex:

The function of the VOR is to stabilise an image on the retina during movement of the head. When the head rotates with a certain speed and direction, the VOR rotates the eyes with the same speed in the opposite direction. The combination of head and eye rotation (i.e., the eye’s rotation in space), is ideally near zero. In condition that effect motor function and balance, the VOR is distorted. Total task time = 2 mintues. Key measures: eye to head rotation ratio.
Timepoint [10] 390040 0
baseline - week prior to commencement of intervention
follow up - 12 weeks after intervention commencement
Secondary outcome [11] 390041 0
Cognitive ocular motor control 1) Simon task:

Modulates cognitive processing requirements by introducing conflict between the location of a stimulus and the direction of the response it elicits (correspondence effect). When the spatial location of the stimulus and the direction of the movement required do not match (incongruent), conflict is created between the automatically generated response elicited by the stimulus location (direct pathway) and the required response (indirect pathway). Typically, responses for incongruent trials are slower than congruent trials, where stimulus location direction matches the required movement. This is theoretically due to the extra requirement of inhibiting the automatic, but incorrect, response and facilitating the correct response. Task efficiency, another measure of cognitive processing, is measurable as the magnitude of the correspondence effect (incongruent trial latency minus congruent trial latency: Simon effect). The Simon effect is typically larger when a previous trial is congruent compared to when a previous trial is incongruent (i.e. the Simon effect is sequentially modulated). The Simon effect is also modulated by changes in the speed of a response, the effect normally fading for longer response times. The later effect can be interrogated through distributional analyses that reveal the modulation of Simon effect as a function of response time. Total task time: 5 minutes, 128 trials. Key measures: latency, Simon effect
Timepoint [11] 390041 0
baseline - week prior to commencement of intervention
follow up - 12 weeks after intervention commencement
Secondary outcome [12] 390042 0
Cognitive ocular motor control 2) Interleaved – Task switching:

Experimentally, the assessment of processes associated with flexible and adaptive behaviour, may occur through task switching paradigms. Fundamentally, these paradigms require a participant to respond in one of two ways depending on the type of stimulus presented, creating two different types of tasks. Trials prompting these different tasks are typically interleaved pseudo-randomly, with successive trials either requiring the repetition of the same task (repeat trials), or requiring a change from one task to another (switch trials). Generally, performance is poorer for switch trials compared to repeat trials (switch cost), with a larger switch cost considered indicative of poorer task switching ability. For this task, the dominant response of looking towards a suddenly appearing peripheral stimulus (prosaccade) and the more cognitively difficult, non-dominant response of looking away from a peripheral stimulus (antisaccade). Total task time: 5 minutes. Key measures: latency, error, switch cost.
Timepoint [12] 390042 0
baseline - week prior to commencement of intervention
follow up - 12 weeks after intervention commencement
Secondary outcome [13] 390043 0
Grip strength will be tested by gripping an electric grip strength dynamometer which measures the force in kilograms.
Timepoint [13] 390043 0
baseline - week prior to commencement of intervention
follow up - 12 weeks after intervention commencement

Eligibility
Key inclusion criteria
1. Diagnosis of Parkinson’s Disease or Atypical Parkinsonism
2. Stage 2, 3 or 4 on the Hoehn and Yahr scale
3. Ability to speak English
4. Willingness and ability to provide written informed consent
5. Willingness and ability to attend twice weekly intervention sessions for 12 weeks.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

1. Significant dyskinesia
2. Significant motor fluctuations
3. Myasthenia Gravis, Charcot-Marie Tooth disease, Post-Polio Sundrome, Guillain–Barré syndrome, Fibromyalgia, herniated disk, osteoarthritis of the spine.
4. Diagnosis of dementia
5. Cognitive impairment that prevents patient from provided informed consent in the opinion of the recruiting study doctor.
6. Unable to undergo physical testing or ocular motor testing
7. Unstable or life-threatening disease or illness that could lead to difficulty complying with the protocol
8. Medical condition that contraindicates physical activity
9. Severe visual or auditory impairment
10. History of chronic alcohol abuse within the past 5 years
11. Unable to attend the follow-up assessments
12. Diagnosis of neurological disorder affecting balance
13. Diagnosis of muscular disorder affecting balance

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)
Allocation involved contacting the holder of the allocation schedule who was at central administration site.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
First stratified into Parkinson's and Atypical Parkinsonism.
The randomised to one of two groups using the method of randomly permuted blocks of size 4.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Mixed effects ANOVA

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
10/09/2019
Date of last participant enrolment
Anticipated
1/06/2021
Actual
13/10/2021
Date of last data collection
Anticipated
6/09/2021
Actual
13/01/2022
Sample size
Target
30
Accrual to date
Final
30
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 18047 0
The Alfred - Melbourne
Recruitment postcode(s) [1] 32025 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 300041 0
Government body
Name [1] 300041 0
Department of Industry Innovation and Science
Country [1] 300041 0
Australia
Funding source category [2] 307239 0
Commercial sector/Industry
Name [2] 307239 0
Isodynamics Corporation Pty. Ltd.
Country [2] 307239 0
Australia
Primary sponsor type
University
Name
Monash University
Address
Monash University
Clayton
Victoria 3800
Australia
Country
Australia
Secondary sponsor category [1] 307845 0
None
Name [1] 307845 0
Address [1] 307845 0
Country [1] 307845 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300888 0
The Alfred Ethics Committee
Ethics committee address [1] 300888 0
Ethics committee country [1] 300888 0
Australia
Date submitted for ethics approval [1] 300888 0
09/01/2019
Approval date [1] 300888 0
29/03/2019
Ethics approval number [1] 300888 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 85166 0
Prof Terence O'Brien
Address 85166 0
Central Clinical School
The Alfred Centre
99 Commercial Road
Prahran
3004
VIC
Country 85166 0
Australia
Phone 85166 0
+61399030855
Fax 85166 0
Email 85166 0
[email protected]
Contact person for public queries
Name 85167 0
Ben Sinclair
Address 85167 0
Central Clinical School
The Alfred Centre
99 Commercial Road
Prahran
3004
VIC
Country 85167 0
Australia
Phone 85167 0
+61415314218
Fax 85167 0
Email 85167 0
[email protected]
Contact person for scientific queries
Name 85168 0
Benjamin Sincair
Address 85168 0
Central Clinical School
The Alfred Centre
99 Commercial Road
Prahran
3004
VIC
Country 85168 0
Australia
Phone 85168 0
+61415314218
Fax 85168 0
Email 85168 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Group allocation and outcome measures (anonymised)
When will data be available (start and end dates)?
From publication of trial, available for 5 years after publication
Available to whom?
University partners undertaking multi-site studies.
Available for what types of analyses?
Meta-analyses. Mega-analyses
How or where can data be obtained?
Communication with principle investigator Terry O'Brien or research coordinator Ben Sinclair.
[email protected]
[email protected]


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
9777Study protocol  [email protected]
9778Statistical analysis plan  [email protected]
9779Informed consent form  [email protected]
9780Ethical approval  [email protected]



Results publications and other study-related documents

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