ANZCTR - Registration

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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

6/06/2022

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]

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

Spinocerebellar Ataxia

Recessively or dominantly inherited cerebellar ataxia

Condition category

Condition code

Neurological

Neurodegenerative diseases

Human Genetics and Inherited Disorders

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]

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]

Motor domain of the Functional Independence Measure score

Timepoint [1]

Baseline (immediately prior to rehabilitation/control period), six weeks after baseline, 18 weeks after baseline, 30 weeks after baseline (primary timepoint).

Secondary outcome [1]

Scale for the Assessment and Rating of Ataxia

Timepoint [1]

Baseline (immediately prior to rehabilitation/control period), six weeks after baseline, 18 weeks after baseline, 30 weeks after baseline.

Secondary outcome [2]

Berg Balance Scale

Timepoint [2]

Baseline (immediately prior to rehabilitation/control period), six weeks after baseline, 18 weeks after baseline, 30 weeks after baseline.

Secondary outcome [3]

Medical Outcomes Study 36 item Short-Form Health Survey Version 2 (SF-36 V2)

Timepoint [3]

Baseline (immediately prior to rehabilitation/control period), six weeks after baseline, 18 weeks after baseline, 30 weeks after baseline.

Secondary outcome [4]

Patient Global Impression of Change scale

Timepoint [4]

Six weeks after baseline (immediately after outpatient rehabilitation/six weeks of control period), 18 weeks after baseline, 30 weeks after baseline.

Secondary outcome [5]

Function in Sitting Test

Timepoint [5]

Six weeks after baseline (immediately after outpatient rehabilitation/six weeks of control period), 18 weeks after baseline, 30 weeks after baseline.

Secondary outcome [6]

Daily Step Activity with Fitbit Flex 2.

Timepoint [6]

Baseline (immediately prior to rehabilitation/control period), six weeks after baseline, 18 weeks after baseline, 30 weeks after baseline.

Secondary outcome [7]

Fatigue Severity Scale

Timepoint [7]

Baseline and then fortnightly for duration of the study.

Secondary outcome [8]

Number and history of falls will be recorded via telephone, email or face-to-face physiotherapy visits.

Timepoint [8]

Baseline and then fortnightly for duration of the study.

Secondary outcome [9]

Pain as measured by a Visual Analogue Scale

Timepoint [9]

Baseline and then fortnightly for duration of the study.

Secondary outcome [10]

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]

This information will be gathered weekly by the participant or the participant's carer

Secondary outcome [11]

Sitting and standing balance using the BioKin, an inertial measurement unit.

Timepoint [11]

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

Sex

Both males and females

Can healthy volunteers participate?

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

20/02/2019

Actual

12/04/2019

Date of last participant enrolment

Anticipated

1/08/2022

Actual

Date of last data collection

Anticipated

28/02/2023

Actual

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

NSW,NT,WA,VIC

Recruitment hospital [1]

Monash Medical Centre - Clayton campus - Clayton

Recruitment hospital [2]

Caulfield Hospital - Caulfield

Recruitment hospital [3]

Royal Perth Hospital - Perth

Recruitment hospital [4]

Royal North Shore Hospital - St Leonards

Recruitment hospital [5]

Palmerston Regional Hospital - Holtze

Recruitment hospital [6]

The Royal Childrens Hospital - Parkville

Recruitment hospital [7]

Royal Melbourne Hospital - City campus - Parkville

Recruitment hospital [8]

Concord Repatriation Hospital - Concord

Recruitment postcode(s) [1]

3168 - Clayton

Recruitment postcode(s) [2]

3162 - Caulfield

Recruitment postcode(s) [3]

6000 - Perth

Recruitment postcode(s) [4]

2065 - St Leonards

Recruitment postcode(s) [5]

0829 - Holtze

Recruitment postcode(s) [6]

3052 - Parkville

Recruitment postcode(s) [7]

3050 - Parkville

Recruitment postcode(s) [8]

2139 - Concord

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

Medical Research Future Fund

Address [1]

Department of Health, Sirius Building, Furzer Street, Woden Town Centre, ACT, 2606

Country [1]

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]

None

Name [1]

None

Address [1]

None

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Monash Health HREC

Ethics committee address [1]

Monash Medical Centre, Clayton Road, Clayton 3068

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

20/06/2018

Approval date [1]

08/08/2018

Ethics approval number [1]

HREC/18/MonH/418

Ethics committee name [2]

Northern Territory Department of Health and Menzies School of Health Research

Ethics committee address [2]

Menzies School of Health Research
Royal Darwin Hospital Campus
Rocklands Drive
Casuarina NT 0810 Australia

Ethics committee country [2]

Australia

Date submitted for ethics approval [2]

03/09/2019

Approval date [2]

18/02/2020

Ethics approval number [2]

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

Dr Sarah Milne

Address

Murdoch Children's Research Institute, 50 Flemington Road, Parkville, VIC 3052

Country

Australia

Phone

+61 401960254

Fax

[email protected]

Contact person for public queries

Name

Dr Sarah Milne

Address

Murdoch Children's Research Institute, 50 Flemington Road, Parkville, VIC 3052

Country

Australia

Phone

+61 401960254

Fax

[email protected]

Contact person for scientific queries

Name

Dr Sarah Milne

Address

Murdoch Children's Research Institute, 50 Flemington Road, Parkville, VIC 3052

Country

Australia

Phone

+61 401960254

Fax

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

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?

Current supporting documents:

Updated to:

Doc. No.	Type	Citation	Link	Email	Other Details	Attachment
23632	Statistical analysis plan	Grobler, Anneke; Milne, Sarah (2023). Statistical analysis plan for The efficacy of rehabilitation for hereditary cerebellar ataxia trial. Murdoch Childrens Research Institute. Online resource. https://doi.org/10.25374/MCRI.23559330.v1	https://mcri.figshare.com/articles/online_resource/Statistical_analysis_plan_for_The_efficacy_of_rehabilitation_for_hereditary_cerebellar_ataxia_trial/23559330/1	[email protected]
23633	Informed consent form	Milne SC, Corben LA, Roberts M, et alRehabilitation for ataxia study: protocol for a randomised controlled trial of an outpatient and supported home-based physiotherapy programme for people with hereditary cerebellar ataxiaBMJ Open 2020;10:e040230. doi: 10.1136/bmjopen-2020-040230	https://doi.org/10.1136/bmjopen-2020-040230	[email protected]

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Rehabilitation for ataxia study: Protocol for a randomised controlled trial of an outpatient and supported home-based physiotherapy programme for people with hereditary cerebellar ataxia.	2020	https://dx.doi.org/10.1136/bmjopen-2020-040230

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Documents added manually

Documents added automatically