Trial Review

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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
2/06/2024
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: 4-6 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 ACTRN12612001269820 (Australian CP-Child)

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 6 years 3 months corrected age (CA) follow-up at one time point, combining 4 RCTs of infants recruited <6 months CA (1-4) or participated in other early-intervention studies (5). School readiness outcomes will be prepared to an historical cohort of children from the Australian CP Child study (6) who were diagnosed >2 years and 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) Preschool HABIT-ILE (ACTRN12620000071921, n=60): A randomised controlled trial to determine efficacy of intensive rehabilitation compared to usual care to improve motor skills of children aged 2-5 years, with bilateral cerebral palsy.
(6) Australian CP-Child (ACTRN12612001269820, n=245): a prospective cohort study of motor development and brain structure in young children, with cerebral palsy born in Queensland in 2006, 2007, 2008 and 2009.

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 (ACTRN12612001269820, 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 - 6 years 3 months corrected age.
Secondary outcome [2] 397457 0
Pediatric Evaluation of Disability Inventory Computerised Assessment Test (PEDI-CAT)
Timepoint [2] 397457 0
4 years - 6 years 3 months corrected age
Secondary outcome [3] 397458 0
Behaviour Rating Inventory of Executive Function -Preschool (BRIEF-P)
Timepoint [3] 397458 0
4 years - 6 years 3 months corrected age
Secondary outcome [4] 397466 0
The Infant Toddler Quality of Life Questionnaire (ITQOL)
Timepoint [4] 397466 0
4 years - 6 years 3 months corrected age
Secondary outcome [5] 397467 0
Health Resource Usage Questionnaire
Timepoint [5] 397467 0
4 years - 6 years 3 months corrected age
Secondary outcome [6] 397469 0
Behaviour Assessment System for Children (BASC-3)
Timepoint [6] 397469 0
4 years - 6 years 3 months corrected age
Secondary outcome [7] 397471 0
Emotional Availability-Self Report (EA-SR) questionnaire
Timepoint [7] 397471 0
4 years - 6 years 3 months corrected age
Secondary outcome [8] 397472 0
Depression Anxiety Stress Scales (DASS-21)
Timepoint [8] 397472 0
4 years - 6 years 3 months corrected age
Secondary outcome [9] 397473 0
Peabody Developmental Motor Skills (PDMS-2)
Timepoint [9] 397473 0
4 years - 6 years 3 months corrected age
Secondary outcome [10] 397474 0
Habitual Physical Activity (HPA)
Timepoint [10] 397474 0
4 years - 6 years 3 months corrected age
Secondary outcome [11] 397477 0
The life Events List
Timepoint [11] 397477 0
4 years - 6 years 3 months corrected age
Secondary outcome [12] 397612 0
Body composition using bio-electrical impedance analysis (BIA)
Timepoint [12] 397612 0
4 years - 6 years 3 months corrected age
Secondary outcome [13] 397616 0
Preschool Language School-5 (PLS-5)
Timepoint [13] 397616 0
4 years - 6 years 3 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 - 6 years 3 months corrected age
Secondary outcome [15] 398474 0
Center for Youth Wellness (CYW) Adverse Childhood Experiences Questionnaire
Timepoint [15] 398474 0
4 years - 6 years 3 months corrected age
Secondary outcome [16] 399711 0
Body weight
Timepoint [16] 399711 0
4 years - 6 years 3 months corrected age
Secondary outcome [17] 399712 0
height
Timepoint [17] 399712 0
4 years - 6 years 3 months corrected age
Secondary outcome [18] 399713 0
Knee height
Timepoint [18] 399713 0
4 years - 6 years 3 months corrected age
Secondary outcome [19] 399714 0
Small Kids Assisting Hand Assessment (AHA
Timepoint [19] 399714 0
4 years - 6 years 3 months corrected age
Secondary outcome [20] 399715 0
Both Hands Assessment (BoHA)
Timepoint [20] 399715 0
4 years - 6 years 3 months corrected age
Secondary outcome [21] 417015 0
Australian Eating Survey Food Frequency Questionnaire )AES-FFQ)
Timepoint [21] 417015 0
4 years - 6 years 3 months corrected age
Secondary outcome [22] 417016 0
Dysphagia Disorder Survey (DDS)
Timepoint [22] 417016 0
4 years - 6 years 3 months
Secondary outcome [23] 417017 0
3-oz water drinking test
Timepoint [23] 417017 0
4 years - 6 years 3 months

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), Protect Me (ACTRN12617001515381) and Preschool HABIT-ILE (ACTRN12620000071921) Clinical Trials;
(b) aged > 2 yrs (between 4 years to 6 years and 3 months corrected age (CA) at the time of assessment);
(c) able to attend testing sessions;
Minimum age
48 Months
Maximum age
75 Months
Sex
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
Recruiting
Date of first participant enrolment
Anticipated
20/09/2021
Actual
24/01/2022
Date of last participant enrolment
Anticipated
20/12/2025
Actual
Date of last data collection
Anticipated
20/12/2025
Actual
Sample size
Target
425
Accrual to date
93
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,WA,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 hospital [4] 23743 0
Perth Children's Hospital - Nedlands
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
Recruitment postcode(s) [4] 39186 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 26166 0
United States of America
State/province [1] 26166 0
Ohio

Funding & Sponsors
Funding source category [1] 308997 0
Government body
Name [1] 308997 0
Australian Government Department of Health
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
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
Ethics committee name [2] 315071 0
The University of Sydney Human Research Ethics Committee
Ethics committee address [2] 315071 0
Ethics committee country [2] 315071 0
Australia
Date submitted for ethics approval [2] 315071 0
15/09/2021
Approval date [2] 315071 0
23/12/2021
Ethics approval number [2] 315071 0
2021/835
Ethics committee name [3] 315072 0
Ohio State Behavioral and Social Sciences Institutional Review Board
Ethics committee address [3] 315072 0
Ethics committee country [3] 315072 0
United States of America
Date submitted for ethics approval [3] 315072 0
26/10/2023
Approval date [3] 315072 0
10/01/2024
Ethics approval number [3] 315072 0
2023B0230

Summary
Brief summary
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
[email protected]
Contact person for public queries
Name 112227 0
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
[email protected]
Contact person for scientific queries
Name 112228 0
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
[email protected]

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?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
21733Study protocolBoyd RN, Novak I, Morgan C, Bora S, Sakzewski L, Ware RS, Comans T, Fahey MC, Whittingham K, Trost S, Pannek K, Pagnozzi A, Mcintyre S, Badawi N, Smithers Sheedy H, Palmer KR, Burgess A, Keramat A, Bell K, Hines A, Benfer K, Gascoigne-Pees L, Leishman S, Oftedal S. School readiness of children at high risk of cerebral palsy randomised to early neuroprotection and neurorehabilitation: protocol for a follow-up study of participants from four randomised clinical trials. BMJ Open. 2023 Feb 27;13(2):e068675. doi: 10.1136/bmjopen-2022-068675. PMID: 36849209; PMCID: PMC9972445.https://www.pubmed.ncbi.nlm.nih.gov/36849209/  



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.