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Trial registered on ANZCTR


Registration number
ACTRN12612000694819
Ethics application status
Approved
Date submitted
20/06/2012
Date registered
29/06/2012
Date last updated
27/11/2018
Date data sharing statement initially provided
27/11/2018
Date results provided
27/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Does outpatient physical rehabilitation improve or maintain functional independence for people with Friedreich ataxia?
Scientific title
What is the effect of an six-week outpatient rehabilitation program compared to a wait-list control on functional independence in people with Friedreich ataxia?
Secondary ID [1] 280687 0
nil
Universal Trial Number (UTN)
nil
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Friedreich ataxia 286715 0
Condition category
Condition code
Neurological 287016 287016 0 0
Neurodegenerative diseases
Human Genetics and Inherited Disorders 287117 287117 0 0
Other human genetics and inherited disorders
Physical Medicine / Rehabilitation 287118 287118 0 0
Physiotherapy

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
An individualised rehabilitation program, consisting of a minimum of 2 hours and 15 minutes of therapy (physiotherapy, exercise physiology and/or allied health assistant supervised exercise therapy and aquatic physiotherapy), 3 times per week as per usual clinical care. In order to provide an individualised rehabilitation program, the treating physiotherapist will conduct a thorough assessment of the participant’s function and impairments. The treating physiotherapist will get access to outome measures, including the Goal Attainment Scale from the first blinded-assessment in order to individualise the rehabilitation program to the participant’s specific goals. rehabilitation will be broken down into domains in order to address the specific impairments which may contribute to functional decline. Rehabilitation will be separated into seven ‘domains’: coordination and control exercises, functional mobility, strengthening, cardiovascular fitness and muscle endurance, core-stability, balance training, and stretching. Sessions may be one-on-one, in a group setting or a combination of both. In addition, a home exercise program (HEP) will be given to the participant, to be commenced immediately after the period of intervention, as per standard practice. The home exercise program will consist of any of/or a combination of aquatic exercises, home based exercises or a gym program. This content will be determined by participant and rehabilitation/treating physiotherapist. The HEP will be prescribed during the intervention
Intervention code [1] 285123 0
Rehabilitation
Comparator / control treatment
Wait-list control: where participants are added to a wait-list to receive rehabilitation within the standard average time frame of six weeks. After the wait-list control period participants will receive the same intervention as per the intervention group. During the wait-list period participants will still have access to standard care, however participants will be asked not to increase their exercise/therapy over what they were completing on study entry.
Control group
Active

Outcomes
Primary outcome [1] 287350 0
Functional improvement as measured by the Functional Independence Measure (FIM).
Timepoint [1] 287350 0
At baseline, week 6, week 12, week 18 and week 24 after baseline. (Baseline is two weeks after randomisation.)
Primary outcome [2] 287351 0
Disease progression as measured by the Friedreich Ataxia Rating Scale (FARS).
Timepoint [2] 287351 0
At baseline, week 6, week 12, week 18 and week 24 after baseline. (Baseline is two weeks after randomisation.)
Primary outcome [3] 287352 0
Quality of life as measured by the Friedriech Ataxia Impact Scale (FAIS).
Timepoint [3] 287352 0
At baseline, week 6, week 12, week 18 and week 24 after baseline. (Baseline is two weeks after randomisation.)
Secondary outcome [1] 297965 0
Foot posture as assessed by the Foot Posture Index (FPI).
Timepoint [1] 297965 0
At baseline, week 6, week 12, week 18 and week 24 after baseline. (Baseline is two weeks after randomisation.)
Secondary outcome [2] 297966 0
Gastrocnemius, soleus and tibialis posterior spasticity as measured by the Modified Tardieu Scale.
Timepoint [2] 297966 0
At baseline, week 6, week 12, week 18 and week 24 after baseline. (Baseline is two weeks after randomisation.)
Secondary outcome [3] 297967 0
Balance as assessed by the Berg Balance Score.
Timepoint [3] 297967 0
At baseline, week 6, week 12, week 18 and week 24 after baseline. (Baseline is two weeks after randomisation.)
Secondary outcome [4] 297968 0
Gait velocity as measured by the Timed 25 Foot Walk (T25FW).
Timepoint [4] 297968 0
At baseline, week 6, week 12, week 18 and week 24 after baseline. (Baseline is two weeks after randomisation.)
Secondary outcome [5] 297970 0
Patient perceived benefit of intervention as assessed by the Patient's Global Impression of Change (PGIC).
Timepoint [5] 297970 0
At baseline, week 6, week 12, week 18 and week 24 after baseline. (Baseline is two weeks after randomisation.)
Secondary outcome [6] 297971 0
Confounding factors related to exercise out of the trial as assessed by the Phone-Fitt.
Timepoint [6] 297971 0
At baseline, week 6, week 12, week 18 and week 24 after baseline. (Baseline is two weeks after randomisation.)
Secondary outcome [7] 314655 0
Individual goal achievement as measured by the Goal Attainment Scale (GAS)
Timepoint [7] 314655 0
At baseline, week 6, week 12, week 18 and week 24 after baseline. (Baseline is two weeks after randomisation.)
Secondary outcome [8] 314656 0
Spatio-temporal gait parameters as measured by the GAITRite mat. Participants will be asked to walk down the mat six times at their preferred and fast speeds.
Timepoint [8] 314656 0
At baseline, week 6, week 12, week 18 and week 24 after baseline. (Baseline is two weeks after randomisation.)

Eligibility
Key inclusion criteria
1. Homozygosity for a GAA expansion in intron 1 of FXN
2. Aged 15 years and over
3. Able to give informed consent
4. Understand written and verbal English
5. Reduction in functional capacity and/or need for physical rehabilitation intervention
6. Able and willing to participate and attend a six-week outpatient rehabilitation program at the Kingston Centre
7. Have a FARS Functional Staging Score 2-5 (Symptoms present, recognized by patient, but still mild – Confined but can navigate a wheelchair and can perform some activities of daily living that do not require standing or walking)
Minimum age
15 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Compound heterozygotes for a GAA expansion in intron 1 and a point mutation/deletion in FXN
2. Aged under 15 years
3. Acute orthopaedic injury limiting ability to weight-bear
4. Pregnancy
5. Living rurally or interstate with no other means of accommodation
6. Those unable to access the outpatient program due to transport issues
7. Need for immediate physiotherapy intervention for safety reasons (i.e. unable to be waitlisted)
8. Those requiring greater than three days per week of intervention (i.e. need for serial casting, multiple falls at home, pain) as assessed by the Friedreich ataxia Clinic multidisciplinary team
9. Other illness that has acutely reduced functional capacity
10. Received botulinum injections or undergone major orthopaedic surgery in last 6 months

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)
The multidisciplinary team from the specialist multidisciplinary Friedreich ataxia clinic at Monash Medical Centre will complete a screening assessment as part of usual clinical practice. People with Friedreich ataxia identified as having the potential to benefit from rehabilitation will be considered for inclusion in the study. People meeting the inclusion criteria will be invited to participate in the study, will receive comprehensive information about the study and will be asked to sign a written consent form. Once recruited to the study each participant will be randomly assigned to the immediate start ‘intervention’ group or the wait-list ‘control’ group.
A study statistician, independent of the trial, will be responsible for generating (via computer) the allocation sequence and the block size-randomisation. Once the participant is enrolled, the chief investigator will inform the study statistician, of the participant’s name (and their ambulation status for stratification) via email. The independent person will email the allocation, to immediate intervention or control group, to the investigator. The dates of recruitment and randomisation email correspondence will be kept to provide an audit trail of randomisation and allocation concealment.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will be generated by a computer program using permuted blocks with stratification by ambulation status.

A set of random numbers will be used to create an allocation sequence for use by the chief investigator. Potential selection bias will be reduced by using random block sizes, between 2 and 4, and the investigator will be blinded to the size of each block. A study statistician, independent of the trial, will be responsible for generating (via computer) the allocation sequence and the block size-randomisation.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Other
Other design features
Stepped wedge
Phase
Type of endpoint/s
Efficacy
Statistical methods / analysis
The primary outcome measure for the randomised controlled trial is the FIM total. A mixed effects analysis of covariance (ANCOVA) will be conducted including the fixed effects factor variables Group (factor levels: intervention, control) and Time (factor levels: Assessment- baseline and Assessment- 6 weeks) and a random effect term (random intercept) for Study Individual. Participants’ baseline FIM scores will be used as the covariate in the analysis. The primary intervention effect will be estimated along with 95% confidence interval levels. The confidence interval limits will be utilised to draw inference concerning the average intervention effect in the underlying target population: confirmatory Interpretation of the study findings will be conducted with respect to clinical relevance of the range of possibly true mean effects (confidence interval limits) rather than based on p-values. The threshold for clinical relevance will be set at 3 points on the FIM total.

The primary efficacy analysis will follow the intention-to-treat principle, utilising sensitivity analyses employing best– and worst-case missing value imputation scenarios, to assess robustness of the study findings.

Other outcome measures will be compared between groups using the same approach. Further supportive analyses will include additional baseline covariates in the ANCOVA model to account for different routes of intervention assignment such as orthotic prescription and medical management. An exercise intensity-covariate (Phone FITT or number of HEP sessions) will be included in analyses to account for any varied exercise levels.

The mixed-effect ANCOVA models will be used to explore the relationships between the outcome measures at different time points and clinical parameters, in order to predict which clinical parameter may influence performance on outcome measures.

Significance will be recorded as p<0.05. Statistical analysis will be performed using STATA (Version 13; Stata Corporation, College Station, Texas, USA).

An earlier study that investigated the effect of multidisciplinary inpatient rehabilitation compared to no intervention found a significant mean FIM total score change coefficient of 11.43 (SD=7.92) after a period of inpatient rehabilitation as compared to no intervention (Milne et al 2012). With the change coefficient of 11.43 and a standard deviation of 7.92, with use of a two-tailed alpha of 0.05 and power of 0.90 the sample size required is 12 people per group. To allow for dropout, 16 people will be recruited to each group.

Recruitment
Recruitment status
Stopped early
Data analysis
Data analysis is complete
Reason for early stopping/withdrawal
Participant recruitment difficulties
Date of first participant enrolment
Anticipated
8/08/2015
Actual
8/08/2015
Date of last participant enrolment
Anticipated
7/11/2016
Actual
6/08/2016
Date of last data collection
Anticipated
Actual
11/12/2016
Sample size
Target
32
Accrual to date
Final
19
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 3790 0
Kingston Centre - Cheltenham
Recruitment postcode(s) [1] 9671 0
3192 - Cheltenham

Funding & Sponsors
Funding source category [1] 291265 0
Charities/Societies/Foundations
Name [1] 291265 0
Murdoch Childrens Research Institute
Country [1] 291265 0
Australia
Funding source category [2] 291266 0
University
Name [2] 291266 0
Monash University
Country [2] 291266 0
Australia
Primary sponsor type
Individual
Name
Sarah Milne
Address
Physiotherapy Department
Kingston Centre
Warrigal Road
Cheltenham VIC 3192
Country
Australia
Secondary sponsor category [1] 284308 0
None
Name [1] 284308 0
Address [1] 284308 0
Country [1] 284308 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 287468 0
Southern Health Human Research Ethics B
Ethics committee address [1] 287468 0
Ethics committee country [1] 287468 0
Australia
Date submitted for ethics approval [1] 287468 0
02/05/2012
Approval date [1] 287468 0
27/07/2012
Ethics approval number [1] 287468 0
12134B

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

Contacts
Principal investigator
Name 34324 0
Ms Sarah Milne
Address 34324 0
Bruce Lefroy Centre, Murdoch Childrens Research Institute, Flemington Road, Parkville VIC 3052
Country 34324 0
Australia
Phone 34324 0
+61 3 9265 7641
Fax 34324 0
+61 3 9265 2378
Email 34324 0
sarah.milne@mcri.edu.au
Contact person for public queries
Name 17571 0
Sarah Milne
Address 17571 0
Bruce Lefroy Centre, Murdoch Childrens Research Institute, Flemington Road, Parkville VIC 3052
Country 17571 0
Australia
Phone 17571 0
+61 3 9265 7641
Fax 17571 0
Email 17571 0
sarah.milne@mcri.edu.au
Contact person for scientific queries
Name 8499 0
Sarah Milne
Address 8499 0
Bruce Lefroy Centre, Murdoch Childrens Research Institute, Flemington Road, Parkville VIC 3052
Country 8499 0
Australia
Phone 8499 0
+61 3 9265 7641
Fax 8499 0
Email 8499 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
This requirement was not a requirement at the commencement of the study.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.