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Trial registered on ANZCTR


Registration number
ACTRN12618000908235
Ethics application status
Approved
Date submitted
25/05/2018
Date registered
30/05/2018
Date last updated
5/07/2021
Date data sharing statement initially provided
8/02/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Intensive rehabilitation for people with hereditary cerebellar ataxia.
Scientific title
The efficacy of rehabilitation on motor function in individuals with hereditary cerebellar ataxia. A randomised controlled trial.
Secondary ID [1] 294930 0
Nil known
Universal Trial Number (UTN)
U1111-1214-2471
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Friedreich ataxia 307890 0
Spinocerebellar Ataxia 307891 0
Recessively or dominantly inherited cerebellar ataxia 316457 0
Condition category
Condition code
Neurological 306938 306938 0 0
Neurodegenerative diseases
Human Genetics and Inherited Disorders 307115 307115 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention involves a six-week outpatient rehabilitation program followed by a 24-week supported home exercise program. The individualised rehabilitation is targeted at improving motor function, mobility and balance and the home exercise program has been designed to enhance completion of the program. The outpatient program will consist of two hours of rehabilitation provided by a physiotherapist, three times per week. Therapy will be one-on-one. This will be held in a public hospital physiotherapy gym and hydrotherapy pool. The home exercise program will require participants to exercise for one hour, five days per week. The home exercise program will be supported by monthly remote supervision, via telephone or video applications, alternating with fortnightly home visits by the physiotherapist. Participants will be required to record exercise completion with a participant diary and will be asked about their exercise completion at each fortnightly physiotherapy session.
The rehabilitation (both outpatient and home-based) will be based on multi-faceted individualised rehabilitation designed on six domains of rehabilitation: strengthening, sensory stimulation, balance training, postural control, coordination and control and functional mobility. A specific time is allocated to each domain. A list of therapy options within each domain is provided for the treating physiotherapists to select from.
The physiotherapist will assess each individual at the beginning of the intervention to ensure the chosen therapy options are appropriate for (i) the participant’s capacity and impairments; (ii) the environment of the home exercise program; (iii) the specific needs of each participant; and (iv) the feasibility of successfully delivering the rehabilitation at the site. Exercises will be progressed according to the individual’s performance of each exercise, their fatigue and motivation levels, and their goals.
Intervention code [1] 301243 0
Rehabilitation
Comparator / control treatment
Standard care - participants will be asked to continue their current physiotherapy/exercise regime for the duration of the study. This may vary based on their level of physiotherapy/exercise participation on enrolment into the study.
Control group
Active

Outcomes
Primary outcome [1] 305926 0
Motor domain of the Functional Independence Measure score
Timepoint [1] 305926 0
Baseline (immediately prior to rehabilitation/control period), six weeks after baseline, 18 weeks after baseline, 30 weeks after baseline (primary timepoint).
Secondary outcome [1] 347041 0
Scale for the Assessment and Rating of Ataxia
Timepoint [1] 347041 0
Baseline (immediately prior to rehabilitation/control period), six weeks after baseline, 18 weeks after baseline, 30 weeks after baseline.
Secondary outcome [2] 347042 0
Berg Balance Scale
Timepoint [2] 347042 0
Baseline (immediately prior to rehabilitation/control period), six weeks after baseline, 18 weeks after baseline, 30 weeks after baseline.
Secondary outcome [3] 347043 0
Medical Outcomes Study 36 item Short-Form Health Survey Version 2 (SF-36 V2)
Timepoint [3] 347043 0
Baseline (immediately prior to rehabilitation/control period), six weeks after baseline, 18 weeks after baseline, 30 weeks after baseline.
Secondary outcome [4] 347044 0
Patient Global Impression of Change scale
Timepoint [4] 347044 0
Six weeks after baseline (immediately after outpatient rehabilitation/six weeks of control period), 18 weeks after baseline, 30 weeks after baseline.
Secondary outcome [5] 347048 0
Function in Sitting Test
Timepoint [5] 347048 0
Six weeks after baseline (immediately after outpatient rehabilitation/six weeks of control period), 18 weeks after baseline, 30 weeks after baseline.
Secondary outcome [6] 347049 0
Daily Step Activity with Fitbit Flex 2.
Timepoint [6] 347049 0
Baseline (immediately prior to rehabilitation/control period), six weeks after baseline, 18 weeks after baseline, 30 weeks after baseline.
Secondary outcome [7] 347050 0
Fatigue Severity Scale
Timepoint [7] 347050 0
Baseline and then fortnightly for duration of the study.
Secondary outcome [8] 347051 0
Number and history of falls will be recorded via telephone, email or face-to-face physiotherapy visits.
Timepoint [8] 347051 0
Baseline and then fortnightly for duration of the study.
Secondary outcome [9] 347052 0
Pain as measured by a Visual Analogue Scale
Timepoint [9] 347052 0
Baseline and then fortnightly for duration of the study.
Secondary outcome [10] 366626 0
Health economic analysis as measured by SF6D, weekly carer hours required for activities of daily living and transport and new equipment purchased during the trial related to activities of daily living. This information will be obtained by the participant or the participant's carer's verbal report.
Timepoint [10] 366626 0
This information will be gathered weekly by the participant or the participant's carer
Secondary outcome [11] 366627 0
Sitting and standing balance using the BioKin, an inertial measurement unit.
Timepoint [11] 366627 0
Baseline (immediately prior to rehabilitation/control period), six weeks after baseline, 18 weeks after baseline and 30 weeks after baseline.

Eligibility
Key inclusion criteria
1. Have a molecular diagnosis or at least three generations affected, of a recessive or dominant inherited cerebellar ataxia.
2. Aged over 15 years
3. A minimum score of 2 for question 1: Gait of the Scale for the Assessment and Rating of Ataxia (SARA) [2 = Gait clearly abnormal, tandem walking > 10 steps not possible].
4. A minimum score of 4 for item I: Transfers Bed, Chair, Wheel-chair of the Functional Independence Measure [4 = Minimal Assistance, the participant completes 75% or more of the task].
5. Given clearance by cardiologist or other appropriate medical professional for participation in rehabilitation and the hydrotherapy component.
6. Able to give informed consent.
Minimum age
15 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Individuals with non-genetic ataxia or non-degenerative ataxia.
2. Musculoskeletal injury limiting ability to weight-bear.
3. Another medical condition not related to their hereditary cerebellar ataxia that impacts on mobility.
4. Undergone major orthopaedic surgery in the last six months.
5. Need for immediate intensive intervention for safety reasons.
6. Pregnancy.
7. Dementia or significant cognitive impairment limiting ability to give informed consent and participate in the rehabilitation program.
8. Received botulinum toxin injections for spasticity management (except for regular longstanding paraspinal botulinum injections - this is defined as at least two doses of botulinum injections in the same muscle/s within eight months of the screening period).
9. Already completing greater than three hours per week physical exercise/therapy focused on the lower limb (i.e. pilates, personal trainer, home exercise program, independent gym program, exercise physiology) or is participating in a structured goal-based physiotherapy rehabilitation program. This does not include physical activity that occurs as part of the person's daily life, i.e. walking to the shops.
10. Currently enrolled in a clinical trial or planned enrolment in a clinical trial during the period of the study.
11. Has a medical condition that precludes entry into a hydrotherapy pool, including bowel incontinence.

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)
An independent statistician will create random allocation tables using block randomisation. These will be provided to the Research Electronic Data Capture (REDCap) administrator to be uploaded to the REDCap randomisaton tool. The allocation will be concealed from investigators enrolling the participants and access to the allocation tables on REDCap will be blocked from the enrolling investigators.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will be via a computer-generated set of random numbers utilising the REDCap randomization tool. An independent statistician will create random allocation tables using block randomisation with random block sizes of two and four. The statistician will generate the random allocation tables.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
The sample size calculation will be based on a 2.5-point improvement in the motor domain of the Functional Independence Measure (m-FIM). Assuming a 15% drop out at 30 months, using a 2-tailed type I error of 5% with 80% power, 40 participants per group are required to detect an increase of the m-FIM by 2.5 points (SD=3.3) in the intervention versus 0.0 (SD=3.9) in the control group.
As there is no documented Minimal Clinically Important Difference (MCID) in any outcomes measuring function in the hereditary cerebellar ataxias, a change of 4-points on the m-FIM has been determined as clinically relevant. A four-point change in the m-FIM relates to an improvement in independence on four activities of daily living. As this study is powered to detect a statistically significant change of 2.5-points, it will also be powered to detect a four-point improvement in the m-FIM.
Data analysis: A repeated measures mixed-effects linear regression model will be used, including the fixed effects group (intervention, control) and time (baseline, assessment week 6, 18 and 30) and stratification variable (site) and a random effect for individual study participants to analyse the effect of treatment group for each of the dependent continuous variables. The primary efficacy analysis will follow the intention-to-treat principle. The intervention effect on the primary outcome, m-FIM, will be estimated along with 95% confidence interval levels. Transformations or non-parametric methods will be used to compare outcomes in the two treatment arms for skewed data. Subgroup analyses will be conducted in participants with and without sensory impairment and with and without vestibular pathology.

A cost-effectiveness analysis will be conducted to evaluate the outpatient physiotherapy intervention compared to usual care. Participants’ quality of life will be incorporated through use of the SF6D measure derived from the SF-36, which generates utility measures suitable for use in economic evaluation. Costs of the intervention will be estimated based on the study protocol and budget. Cost associated with carer hours and personal equipment purchased will be estimated via self-report. An incremental cost per QALY for the intervention group relative to control will be reported. Extensive one way and probabilistic sensitivity analyses will be conducted.

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,NT,WA,VIC
Recruitment hospital [1] 10920 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment hospital [2] 10921 0
Caulfield Hospital - Caulfield
Recruitment hospital [3] 10923 0
Royal Perth Hospital - Perth
Recruitment hospital [4] 10924 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [5] 13075 0
Palmerston Regional Hospital - Holtze
Recruitment hospital [6] 16003 0
The Royal Childrens Hospital - Parkville
Recruitment hospital [7] 16004 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [8] 16005 0
Concord Repatriation Hospital - Concord
Recruitment postcode(s) [1] 22691 0
3168 - Clayton
Recruitment postcode(s) [2] 22692 0
3162 - Caulfield
Recruitment postcode(s) [3] 22694 0
6000 - Perth
Recruitment postcode(s) [4] 22695 0
2065 - St Leonards
Recruitment postcode(s) [5] 25583 0
0829 - Holtze
Recruitment postcode(s) [6] 29501 0
3052 - Parkville
Recruitment postcode(s) [7] 29502 0
3050 - Parkville
Recruitment postcode(s) [8] 29503 0
2139 - Concord

Funding & Sponsors
Funding source category [1] 299510 0
Government body
Name [1] 299510 0
Medical Research Future Fund
Address [1] 299510 0
Department of Health, Sirius Building, Furzer Street, Woden Town Centre, ACT, 2606
Country [1] 299510 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
Murdoch Children's Reseach Institute
Address
Murdoch Children's Research Institute, 50 Flemington Road, Parkville, VIC, 3052
Country
Australia
Secondary sponsor category [1] 301657 0
None
Name [1] 301657 0
None
Address [1] 301657 0
None
Country [1] 301657 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300410 0
Monash Health HREC
Ethics committee address [1] 300410 0
Monash Medical Centre, Clayton Road, Clayton 3068
Ethics committee country [1] 300410 0
Australia
Date submitted for ethics approval [1] 300410 0
20/06/2018
Approval date [1] 300410 0
08/08/2018
Ethics approval number [1] 300410 0
HREC/18/MonH/418
Ethics committee name [2] 305477 0
Northern Territory Department of Health and Menzies School of Health Research
Ethics committee address [2] 305477 0
Menzies School of Health Research
Royal Darwin Hospital Campus
Rocklands Drive
Casuarina NT 0810 Australia
Ethics committee country [2] 305477 0
Australia
Date submitted for ethics approval [2] 305477 0
03/09/2019
Approval date [2] 305477 0
18/02/2020
Ethics approval number [2] 305477 0

Summary
Brief summary
This study aims to compare the effectiveness of an intensive rehabilitation program (consisting of a six-week outpatient rehabilitation program followed by a supported home exercise program (HEP)) compared with standard care on motor function in individuals with hereditary cerebellar ataxia. The study will be a multi-centre randomised controlled trial. The intervention group will receive outpatient rehabilitation three days per week for six-weeks followed by 24 weeks of a supported HEP (fortnightly teleconference/home visits), while the control group will be asked to continue their current care for 30 weeks. Rehabilitation will be based on six domains of rehabilitation: strengthening, balance, functional mobility practice, postural control, sensory stimulation and coordination and control, and will include land and aquatic physiotherapy. Assessment will occur at baseline, and six, 18 and 30 weeks after baseline. The primary outcome will be the motor domain of the Functional Independence Measure. Secondary outcomes will measure ataxia symptoms, quality of life, balance and patient perceived benefit.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 83574 0
Dr Sarah Milne
Address 83574 0
Murdoch Children's Research Institute, 50 Flemington Road, Parkville, VIC 3052
Country 83574 0
Australia
Phone 83574 0
+61 3 8341 6442
Fax 83574 0
Email 83574 0
sarah.milne@mcri.edu.au
Contact person for public queries
Name 83575 0
Dr Sarah Milne
Address 83575 0
Murdoch Children's Research Institute, 50 Flemington Road, Parkville, VIC 3052
Country 83575 0
Australia
Phone 83575 0
+61 3 8341 6442
Fax 83575 0
Email 83575 0
sarah.milne@mcri.edu.au
Contact person for scientific queries
Name 83576 0
Dr Sarah Milne
Address 83576 0
Murdoch Children's Research Institute, 50 Flemington Road, Parkville, VIC 3052
Country 83576 0
Australia
Phone 83576 0
+61 3 8341 6442
Fax 83576 0
Email 83576 0
sarah.milne@mcri.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
As the data collected is health and private data, this will not be made publicly available.
What supporting documents are/will be available?
No other documents available
Summary results
No Results