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Trial registered on ANZCTR


Registration number
ACTRN12621001253897
Ethics application status
Approved
Date submitted
19/07/2021
Date registered
16/09/2021
Date last updated
16/09/2021
Date data sharing statement initially provided
16/09/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
School Readiness: Long-term neuroprotection and neurorehabilitation outcomes in children at risk of cerebral palsy
Scientific title
SCHOOL READINESS: 4-5 year old follow-up of randomised trials of Neuroprotection and Neurorehabilitation for children at risk of cerebral palsy

Secondary ID [1] 304637 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record
This record is a long-term follow-up study of ACTRN12617001515381 (PROTECT-ME), ACTRN12617000006347 (GAME), ACTRN12615000180516 (REACH), ACTRN12616000351415 (PACT), and ACTRN12616001488493 (PREDICT-CP)

Health condition
Health condition(s) or problem(s) studied:
Cerebral palsy 322575 0
Condition category
Condition code
Physical Medicine / Rehabilitation 320190 320190 0 0
Other physical medicine / rehabilitation

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
The present study is a 4 years to 5 years 9 months corrected age (CA) follow-up at one time point, combining 4 RCTs of infants recruited <6 months CA (1-4) and CPchild (5) diagnosed >2 years who received CAU:
(1) PROTECT Me (ACTRN12617001515381, n=275): 10mg melatonin versus placebo with CAU
(2) GAME (ACTRN12617000006347, n=300): Goal directed training in a motor enriched environment (i.e. novel neuroplasticity neurorehabilitation) versus CAU
(3) REACH (ACTRN12615000180516, n=98): Baby mCIMT compared to an equal dose of Baby BIM
(4) PACT (ACTRN12616000351415, n=66): online parenting course, using environmental enrichment through enhanced mother infant emotional availability
(5) PREDICT (ACTRN12616001488493, n=245): Implementation of comprehensive surveillance to Predict outcomes for children with Cerebral Palsy
Data will be collected in one of four ways:
• Paper forms
• Online survey platform (REDcap) instead of/in addition to paper forms for Parent Q’s.
• Devices (ActiGraph, photo/video/audio recording devices) owned by sites/organisations (not personal devices)
• Face-to-face assessments with the child
Intervention code [1] 320992 0
Not applicable
Comparator / control treatment
In this new study of extended follow-up at 4 years of age the following data will be collected in studies 1-4, (ACTRN12617001515381, ACTRN12617000006347, ACTRN12615000180516, ACTRN12616000351415, n=717) and compared to data already collected for children born with CP between 1st January 2006 and 31st December 2009 assessed as part of in historical control study 5 (ACTRN12616001488493, n=245) form 2014 to 2019.
Control group
Historical

Outcomes
Primary outcome [1] 328070 0
Wechsler Preschool & Primary Scale of Intelligence (WPPSI-IV A&NZ)
Timepoint [1] 328070 0
4 years - 5 years 9 months corrected age
Primary outcome [2] 328071 0
Gross Motor Function Measure - 66 (GMFM-66)
Timepoint [2] 328071 0
4 years - 5 years 9 months corrected age
Secondary outcome [1] 397456 0
Vineland Adaptive Behavior Scales, Third Edition (Vineland-3)
Timepoint [1] 397456 0
4 years - 5 years 9 months corrected age
Secondary outcome [2] 397457 0
Pediatric Evaluation of Disability Inventory Computerised Assessment Test (PEDI-CAT)
Timepoint [2] 397457 0
4 years - 5 years 9 months corrected age
Secondary outcome [3] 397458 0
Behaviour Rating Inventory of Executive Function -Preschool (BRIEF-P)
Timepoint [3] 397458 0
4 years - 5 years 9 months corrected age
Secondary outcome [4] 397466 0
The Infant Toddler Quality of Life Questionnaire (ITQOL)
Timepoint [4] 397466 0
4 years - 5 years 9 months corrected age
Secondary outcome [5] 397467 0
Health Resource Usage Questionnaire
Timepoint [5] 397467 0
4 years - 5 years 9 months corrected age
Secondary outcome [6] 397469 0
Behaviour Assessment System for Children (BASC-3)
Timepoint [6] 397469 0
4 years - 5 years 9 months corrected age
Secondary outcome [7] 397471 0
Emotional Availability-Self Report (EA-SR) questionnaire
Timepoint [7] 397471 0
4 years - 5 years 9 months corrected age
Secondary outcome [8] 397472 0
Depression Anxiety Stress Scales (DASS-21)
Timepoint [8] 397472 0
4 years - 5 years 9 months corrected age
Secondary outcome [9] 397473 0
Peabody Developmental Motor Skills (PDMS-2)
Timepoint [9] 397473 0
4 years - 5 years 9 months corrected age
Secondary outcome [10] 397474 0
Habitual Physical Activity (HPA)
Timepoint [10] 397474 0
4 years - 5 years 9 months corrected age
Secondary outcome [11] 397477 0
The life Events List
Timepoint [11] 397477 0
4 years - 5 years 9 months corrected age
Secondary outcome [12] 397612 0
Body composition using bio-electrical impedance analysis (BIA)
Timepoint [12] 397612 0
4 years - 5 years 9 months corrected age
Secondary outcome [13] 397616 0
Preschool Language School-5 (PLS-5)
Timepoint [13] 397616 0
4 years - 5 years 9 months corrected age
Secondary outcome [14] 398473 0
Wechsler Individual Achievement Test – Australia and New Zealand Standardised,
Third Edition
Timepoint [14] 398473 0
4 years - 5 years 9 months corrected age
Secondary outcome [15] 398474 0
Center for Youth Wellness (CYW) Adverse Childhood Experiences Questionnaire
Timepoint [15] 398474 0
4 years - 5 years 9 months corrected age
Secondary outcome [16] 398475 0
Bruininks-Oseretsky Test of Motor Proficiency Second Edition (BOT-2)
Timepoint [16] 398475 0
4 years - 5 years 9 months corrected age
Secondary outcome [17] 399711 0
Body weight
Timepoint [17] 399711 0
4 years - 5 years 9 months corrected age
Secondary outcome [18] 399712 0
height
Timepoint [18] 399712 0
4 years - 5 years 9 months corrected age
Secondary outcome [19] 399713 0
Knee height
Timepoint [19] 399713 0
4 years - 5 years 9 months corrected age
Secondary outcome [20] 399714 0
Small Kids Assisting Hand Assessment (AHA
Timepoint [20] 399714 0
4 years - 5 years 9 months corrected age
Secondary outcome [21] 399715 0
Both Hands Assessment (BoHA)
Timepoint [21] 399715 0
4 years - 5 years 9 months corrected age

Eligibility
Key inclusion criteria
INCLUSION CRITERIA
(a) Children diagnosed with CP or at high risk of CP based on their recruitment and follow-up in the REACH (ACTRN12615000180516), GAME (ACTRN12617000006347), EARLY PACT (ACTRN12616000351415) and Protect Me (ACTRN12617001515381) Clinical Trials;
(b) aged > 2 yrs (between 4 years to 5 years and 9 months corrected age (CA) at the time of assessment);
(c) able to attend testing sessions;
Minimum age
48 Months
Maximum age
69 Months
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
None

Study design
Purpose
Duration
Cross-sectional
Selection
Defined population
Timing
Both
Statistical methods / analysis
The total number of participants with data for the primary outcome (WPPSI-IV A&NZ) is expected to be n=383 (conservatively assume 4 years to 5 years 9 months c.a data from 90% of 425 potential participants). This gives 90% power (alpha=0.05) to detect between intervention/CAU differences of 0.26 standard deviations or greater. This is equivalent to a difference of >3.9 units on WPPSI-IV standardised norms. When examined by intervention type, we have 90% power (alpha=0.05) to detect a between-group difference of >6.4 units for neuroprotectants and >4.8 for neurorehabilitation. For ambulant children we can detect between group differences of >5.2 units and >5.5 for non-ambulant children. For secondary outcome GMFM we have >95% power to detect a minimally important clinical difference (MCID) of at least 5 units overall (and >95% power for ambulant (MCID=7), >80% power non-ambulant (MCID=5)).
The association between group (intervention/CAU) and WPPSI-IV will be investigated using a mixed-effects linear regression model with ‘participant’ included as a random effect to account for the non-independence of observations from the same child. Group and time will be included as fixed effects, with a group-by-time interaction. Balance between groups will be investigated and potential confounders included as co-variables. For Aims 2-4, mixed effects models will be constructed: linear models for continuous outcomes, logistic models for dichotomous outcomes and Poisson models for count outcomes. When constructing predictive models important variables will be examined individually, before construction of multivariable models. The final model will be selected using the Bayesian Information Criterion. Model calibration will be tested graphically and internal validation will use bootstrap resampling. Missing data will be treated case-by-case depending on patterns of data missingness, i.e. multiple imputation methods if ‘missing at random’ and pattern-mixture models if ‘not missing at random’. Adjustment for multiple comparisons will be made, bearing in mind type I & II error rates.

Recruitment
Recruitment status
Not yet 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,QLD,VIC
Recruitment hospital [1] 19819 0
Queensland Children's Hospital - South Brisbane
Recruitment hospital [2] 19820 0
Cerebral Palsy Alliance - Allambie Heights
Recruitment hospital [3] 19821 0
Monash Children’s Hospital - Clayton
Recruitment postcode(s) [1] 34507 0
4101 - South Brisbane
Recruitment postcode(s) [2] 34508 0
2100 - Allambie Heights
Recruitment postcode(s) [3] 34509 0
3168 - Clayton

Funding & Sponsors
Funding source category [1] 308997 0
Government body
Name [1] 308997 0
Australian Government Department of Health
Address [1] 308997 0
Department of Health
GPO Box 9848
Canberra ACT 2601
Country [1] 308997 0
Australia
Primary sponsor type
University
Name
Queensland Cerebral Palsy and Rehabilitation Research, Faculty of Medicine, The University of Queensland
Address
Childrens Health Research Centre,
62 Graham Street
South Brisbane
Queensland. 4030
Country
Australia
Secondary sponsor category [1] 309939 0
None
Name [1] 309939 0
Address [1] 309939 0
Country [1] 309939 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308888 0
Children's Health Queensland Hospital and Health Service HREC
Ethics committee address [1] 308888 0
Centre for Children's Health Research
Level 7, 62 Graham Street
South Brisbane, Queensland, 4101
Ethics committee country [1] 308888 0
Australia
Date submitted for ethics approval [1] 308888 0
19/07/2021
Approval date [1] 308888 0
09/08/2021
Ethics approval number [1] 308888 0
HREC/21/QCHQ/77124

Summary
Brief summary
In Australia, Cerebral Palsy is the most common childhood physical disability (1 in 700) resulting in a lifelong complex chronic disability. Historically CP was not confirmed until the second year of life, and as a result early neuroprotection and early intervention were not always provided. In the past 4 years our Australasian Cerebral Palsy Clinical Trials Network, has implemented early detection so that at risk infants have been recruited by equal or less than 6 months corrected age into Randomised Controlled Trials (RCTs) of Neuroprotectants and early Neurorehabilitation to determine if these interventions improve motor and cognitive outcomes at 2 years corrected age (CA) This study enables us to undertake longer term follow-up of school readiness at 4 years to 5 years 9 months CA (prior to commencing school) which is unknown.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 112226 0
Prof Roslyn Boyd
Address 112226 0
Queensland Cerebral Palsy and Rehabilitation Research Centre, Faculty of Medicine, University of Queensland
Centre for Children's Health Research
62 Graham Street
South Brisbane, Queensland 4101
Country 112226 0
Australia
Phone 112226 0
+61 7 3069 7372
Fax 112226 0
Email 112226 0
r.boyd@uq.edu.au
Contact person for public queries
Name 112227 0
Prof Roslyn Boyd
Address 112227 0
Queensland Cerebral Palsy and Rehabilitation Research Centre, Faculty of Medicine, University of Queensland
Centre for Children's Health Research
62 Graham Street
South Brisbane, Queensland 4101
Country 112227 0
Australia
Phone 112227 0
+61 7 3069 7372
Fax 112227 0
Email 112227 0
r.boyd@uq.edu.au
Contact person for scientific queries
Name 112228 0
Prof Roslyn Boyd
Address 112228 0
Queensland Cerebral Palsy and Rehabilitation Research Centre, Faculty of Medicine, University of Queensland
Centre for Children's Health Research
62 Graham Street
South Brisbane, Queensland 4101
Country 112228 0
Australia
Phone 112228 0
+61 7 3069 7372
Fax 112228 0
Email 112228 0
r.boyd@uq.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
All data will be stored with an ID number on it and will not be made available.
What supporting documents are/will be available?
No other documents available
Summary results
No Results