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Trial registered on ANZCTR


Registration number
ACTRN12615001286538
Ethics application status
Approved
Date submitted
24/11/2015
Date registered
26/11/2015
Date last updated
14/12/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
An evaluation of environmental enrichment for young girls with Rett syndrome
Scientific title
What is the effect of an environmentally enriched therapy program on function and health in two to six year old girls with Rett syndrome?
Secondary ID [1] 287973 0
Nil known
Universal Trial Number (UTN)
U1111-1176-8853
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Rett syndrome 296853 0
Condition category
Condition code
Neurological 297084 297084 0 0
Other neurological disorders
Physical Medicine / Rehabilitation 297085 297085 0 0
Physiotherapy

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Each child will be assessed over a baseline period prior to the intervention period. The length of baseline will be determined randomly and will be either 1, 2 or 3 months. Assessments during baseline will be monthly and there will be 2, 3 and 4 assessments for those with a 1, 2 and 3 month baseline period respectively.
The treatment program will be conducted in a therapy centre in Shenzhen, China and will include multiple supported activities within a rich sensori-motor environment and the specific activities used will target individual goals in the development of motor skills. The activities will be characterised by a high volume of practice and physical activity, and biologically, will aim to increase production of Brain Derived Neurotrophic Factor (BDNF). The program’s design is also consistent with Motor Learning Theory, including opportunities for practice, intrinsic and extrinsic feedback, judicious use of rest periods, and performance of tasks in a variety of conditions that provide choice, are developmentally engaging and provide opportunities for cognitive learning. For example, tasks will include a range of motor activities such as transitions, standing and walking and each child will be encouraged to build both skill and endurance. The intervention will be conducted for 2 to 3 hours each morning on five days a week. This will continue over a 6 month period. Sessions will be conducted in small groups. During the therapy sessions, one-on-one supervision will be provided by the physiotherapist. The therapist will record a log of attendance, duration of sessions and the activities practiced. Each therapist-child dyad will work within a small group with one to two other therapist-child dyads to provide additional social stimulation during the treatment sessions.
Intervention code [1] 293316 0
Rehabilitation
Comparator / control treatment
There is no separate control group in this study. However, each child will be assessed over a baseline period and these data will be compared with data collected over the intervention period. Each child will be her own control.
The participants will however form three groups depending on the duration of their baseline period which determined randomly and will be either 1, 2 or 3 months.
Control group
Active

Outcomes
Primary outcome [1] 296687 0
Gross motor function as assessed by the Rett Syndrome Gross Motor Scale
Timepoint [1] 296687 0
Measured at baseline and at 3, 6 and 9 months during the intervention period
Primary outcome [2] 296688 0
Serum levels of BDNF
Timepoint [2] 296688 0
Measured at baseline and 9 months after beginning of intervention
Secondary outcome [1] 319126 0
Quality of sleep using the Sleep Disturbance Scale for Children
Timepoint [1] 319126 0
Measured at baseline and at 3, 6 and 9 months during the intervention period
Secondary outcome [2] 319127 0
Behaviour measured by the Rett Syndrome Behaviour Questionnaire
Timepoint [2] 319127 0
Measured at baseline and at 3, 6 and 9 months during the intervention period
Secondary outcome [3] 319128 0
Constipation measured by family report of child bowel habits
Timepoint [3] 319128 0
Measured at baseline and at 3, 6 and 9 months during the intervention period
Secondary outcome [4] 319129 0
Parent rating of top three concerns for their child’s health and wellbeing on a visual analogue scale
Timepoint [4] 319129 0
Measured at baseline and at 3, 6 and 9 months during the intervention period

Eligibility
Key inclusion criteria
The child will have genetically confirmed Rett syndrome and will be aged between two and six years. Over the previous 12 months, the child will have received no therapy or very low doses of therapy that is less frequent than fortnightly.
Minimum age
2 Years
Maximum age
6 Years
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
The child is older than six years and has been participating in an intensive therapy program over the previous 12 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)
Each child will be randomly allocated to either a 1, 2 or 3 month baseline period. Randomisation will be conducted at a separate site and allocation will be concealed.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will be conducted using the computer program STATA.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
This will be a stepped wedge randomised controlled trial.
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Based on previous data, we estimate a sample size of 12 girls will give us 90% power to identify within-subject gross motor changes with a change of at least 1.2 points on the complex gross motor skills subscale scale of the Rett Syndrome Gross Motor Scale.
The data describing each of the dependent variables over time will be graphed to illustrate levels and trends, and mean values and the inclinations of the slopes for each outcome variable will be compared. We will use linear mixed models to assess the effect of the intervention, taking into account the confounders of time since regression and the type of BDNF polymorphism.

Recruitment
Recruitment status
Completed
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 outside Australia
Country [1] 7357 0
China
State/province [1] 7357 0
Guangdong

Funding & Sponsors
Funding source category [1] 292441 0
Charities/Societies/Foundations
Name [1] 292441 0
Rettsyndrome.org
Address [1] 292441 0
Rettsyndrome.org
P.O. Box 706143
Cincinnati, OH 45270-6143
Country [1] 292441 0
United States of America
Primary sponsor type
University
Name
Telethon Kids Institute
Address
Telethon Kids Institute
PO Box 855
West Perth
Western Australia 6872
Australia
Country
Australia
Secondary sponsor category [1] 291134 0
None
Name [1] 291134 0
Address [1] 291134 0
Country [1] 291134 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293902 0
Human Research Ethics Committee, University of Western Australia
Ethics committee address [1] 293902 0
The University of Western Australia M459,
35 Stirling Highway,
Crawley WA 6009 Australia
Ethics committee country [1] 293902 0
Australia
Date submitted for ethics approval [1] 293902 0
25/08/2015
Approval date [1] 293902 0
05/10/2015
Ethics approval number [1] 293902 0
RA/4/1/7782
Ethics committee name [2] 293903 0
Human Research Ethics Committee, Shenzhen Children's Hospital
Ethics committee address [2] 293903 0
7019, Yitian Road
Fu Tian District
Guangdong Province
Shenzhen
China, 518026
Ethics committee country [2] 293903 0
China
Date submitted for ethics approval [2] 293903 0
07/10/2015
Approval date [2] 293903 0
23/10/2015
Ethics approval number [2] 293903 0
2015[014]

Summary
Brief summary
Girls with Rett syndrome have difficulties performing motor skills. Animal studies have found that the mice with a MECP2 mutation develop better motor skills if their environment is enriched, possibly due to the extra physical activity which then increases production of Brain Derived Neurotrophic Factor (BDNF). BDNF is an important protein for nerve cell growth and maturity. For Rett syndrome, therapies should be more effective if implemented intensively at an early age due not only to inherent brain plasticity and capacity to learn but also potentially due to stimulation of BDNF production. We know that girls with Rett syndrome can learn new skills with training and practice. However, available research studies have involved small numbers of girls with no comparison group or period and we do not know the precise benefits of intensive early intervention in Rett syndrome. This study involves collaboration between researchers and clinicians in Australia and China. Our study will recruit approximately 12 girls younger than 6 years and assess the girls during a period with no intervention and then during an eight to nine month period with environmental enrichment. We will assess motor function, sleep, behaviour, constipation and serum levels of BDNF. Our study will determine the evidence base for intensive environmental enrichment for young girls newly diagnosed with Rett syndrome giving clearer guidance for both clinicians and families
Trial website
None
Trial related presentations / publications
PRESENTATION:
Downs J. Motor development in Rett syndrome, 5th European Rett Syndrome Congress, 2-4 November 2017, Berlin, Germany.
Public notes

Contacts
Principal investigator
Name 61762 0
Dr Jenny Downs
Address 61762 0
Telethon Kids Institute
PO Box 855
West Perth
Perth
Western Australia
6872
Country 61762 0
Australia
Phone 61762 0
+61 9489 7777
Fax 61762 0
Email 61762 0
jenny.downs@telethonkids.org.au
Contact person for public queries
Name 61763 0
Dr Jenny Downs
Address 61763 0
Telethon Kids Institute
PO Box 855
West Perth
Perth
Western Australia
6872
Country 61763 0
Australia
Phone 61763 0
+61 9489 7777
Fax 61763 0
Email 61763 0
jenny.downs@telethonkids.org.au
Contact person for scientific queries
Name 61764 0
Dr Jenny Downs
Address 61764 0
Telethon Kids Institute
PO Box 855
West Perth
Perth
Western Australia
6872
Country 61764 0
Australia
Phone 61764 0
+61 9489 7777
Fax 61764 0
Email 61764 0
jenny.downs@telethonkids.org.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary