Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12620000987965
Ethics application status
Approved
Date submitted
25/05/2020
Date registered
30/09/2020
Date last updated
30/09/2020
Date data sharing statement initially provided
30/09/2020
Type of registration
Retrospectively registered

Titles & IDs
Public title
Understanding the Early Natural History of Cerebral Palsy
Scientific title
Understanding the early natural history of cerebral palsy - a prospective cohort study
Secondary ID [1] 299566 0
1152800 (NHMRC)
Secondary ID [2] 299569 0
PG2116 (CPARF)
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
cerebral palsy 314840 0
Condition category
Condition code
Neurological 313178 313178 0 0
Other neurological disorders

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
This study is an observational study, and there is no intervention involved. The study aims to describe the early natural history of cerebral palsy (CP) by mapping the development of infants with, or at-risk of CP, over the first two years of life. Infants will be recruited before they reach 12 months of age, and will have assessments every 3-6 months until they reach 24 months. Appointments will be conducted by an experienced clinicians in the infant’s home or in centre based sessions. These are standardised assessments that will help track different aspects of development for babies with cerebral palsy, such as: movement and motor abilities, musculoskeletal development, neurodevelopment, vision, sleep, cognition, speech and language development, feeding, social-emotional abilities, parent outcomes, health resource use, general function and demographics. A selection of the following tests will be used in this study: Peabody Developmental Motor Scales-2, Gross Motor Function Measure-66, Hand Assessment for Infants, Mini Assisting Hand Assessment, Assisting Hand Assessment, Gross Motor Function Classification System E&R, Mini-Manual Ability Classification System, Hammersmith Infant Neurological Examination, Neuroimaging (if available), Australian Cerebral Palsy Register Cerebral Palsy Description Form (Part 1), Modified Tardieu Scale, Australian Spasticity Assessment Scale, Hip X-ray (if available), Ricci and Preverbal Visual Assessment, Sleep Disturbance Scale for Children, Pediatric Evaluation of Disability Inventory Computer Adaptive Test, Bayley Scales of Infant and Toddler Development (III or Low Motor Low Vision vsersion) - Cognition, Speech and Language domains, Dysphagia Disorder Survey, Infant Toddler Social Emotional Assessment, Depression Anxiety and Stress Scales-21, Parenting Stress Index, Health Resource Use, Medicare and Pharmaceutical Benefits Scheme data, and Perinatal and socio-demographic information.
Intervention code [1] 315825 0
Diagnosis / Prognosis
Intervention code [2] 315869 0
Early Detection / Screening
Comparator / control treatment
Because this is an observational study, there is no control group.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 321757 0
Neuroimaging (if available as a part of routine clinical care) including cranial ultrasound (assessing anatomical features and categorizing primary brain lesion) and magnetic resonance imaging (assessing anatomical features and categorizing primary brain lesion).

Timepoint [1] 321757 0
Enrolment and 24 months
Primary outcome [2] 321758 0
Hammersmith Infant Neurological Examination
Timepoint [2] 321758 0
3, 6, 9, 12, 18 and/or 24 months
Primary outcome [3] 321759 0
Peabody Developmental Motor Scales-2
Timepoint [3] 321759 0
3, 6, 9, 12, 18 and/or 24 months
Secondary outcome [1] 376134 0
Gross Motor Function Measure-66
Timepoint [1] 376134 0
3, 6, 9, 12, 18 and/or 24 months
Secondary outcome [2] 384020 0
Hand Assessment for Infants
Timepoint [2] 384020 0
3, 6. 9 and/or 12 months
Secondary outcome [3] 384021 0
Mini Assisting Hand Assessment (for hemiplegia only)
Timepoint [3] 384021 0
9, 12 and/or 18 months
Secondary outcome [4] 384022 0
Assisting Hand Assessment (for hemiplegia only)
Timepoint [4] 384022 0
24 months
Secondary outcome [5] 384023 0
Gross Motor Function Classification System Expanded and Revised
Timepoint [5] 384023 0
12, 18 and 24 months
Secondary outcome [6] 384024 0
Mini-Manual Ability Classification System
Timepoint [6] 384024 0
12, 18 and 24 months
Secondary outcome [7] 384025 0
Ricci Assessment (assessment of visual visual function in young infants)
Timepoint [7] 384025 0
Enrolment, 3 months
Secondary outcome [8] 384026 0
Preverbal Visual Assessment
Timepoint [8] 384026 0
6, 9, 12, 18 and/or 24 months
Secondary outcome [9] 384027 0
Sleep Disturbance Scale for Children
Timepoint [9] 384027 0
9, 12, 18 and/or 24 months
Secondary outcome [10] 384028 0
Pediatric Evaluation of Disability Inventory Computer Adaptive Test
Timepoint [10] 384028 0
6, 12, 18 and.or 24 months
Secondary outcome [11] 384029 0
Dynamic muscle length (spasticity) and and muscle contracture (Modified Tardieu Scale)
Timepoint [11] 384029 0
9, 12, 18 and/ or 24 months
Secondary outcome [12] 384030 0
Australian Spasticity Assessment Scale
Timepoint [12] 384030 0
9. 12. 18 and/ or 24 months
Secondary outcome [13] 384031 0
Australian Cerebral Palsy Register Cerebral Palsy Description Form (Part 1)
Timepoint [13] 384031 0
12, 18 and 24 months
Secondary outcome [14] 384032 0
Measure of hip displacement including migration percentage (MP)and acetabular index (AI) on hip X-ray (for children GMFCS Levels III-V) if available
Timepoint [14] 384032 0
18 and 24 months
Secondary outcome [15] 384033 0
Bayley Scales of Infant and Toddler Development (III and/or Low Motor Low Vision version) Cognition Sub Scale
Timepoint [15] 384033 0
6, 12, 18 and/or 24 months
Secondary outcome [16] 384034 0
Bayley Scales of Infant and Toddler Development (III and/or Low Motor Low Vision version) Language Sub Scale
Timepoint [16] 384034 0
9, 12, 18 and/or 24 months
Secondary outcome [17] 384035 0
Dysphagia Disorder Survey
Timepoint [17] 384035 0
18 and 24 months
Secondary outcome [18] 384036 0
Infant Toddler Social Emotional Assessment
Timepoint [18] 384036 0
12, 18 and 24 months
Secondary outcome [19] 384037 0
Depression Anxiety and Stress Scales-21 will be administered with parents only.
Timepoint [19] 384037 0
Enrolment, 12, 18 and/or 24 months
Secondary outcome [20] 384038 0
Parenting Stress Index Short Form-4
Timepoint [20] 384038 0
12, 18 and 24 months
Secondary outcome [21] 384039 0
Health Resource Use using a study specific questionnaire.
Timepoint [21] 384039 0
12 and 24 months
Secondary outcome [22] 384040 0
Medicare claims history and Pharmaceutical Benefits Scheme (PBS) claims history (individual utilisation and cost data). Data will be collected using approved consented access and data extraction as per Medicare Australia guidelines.


Timepoint [22] 384040 0
24 months
Secondary outcome [23] 386935 0
Child perinatal demographics using study specific questionnaire conducted by interview with parent or carer and review of medical records. Child demographic data will include:
Gestational age
Child perinatal risk factors for cerebral palsy
Birth anthropometrics
Perinatal health conditions
Timepoint [23] 386935 0
Enrolment
Secondary outcome [24] 386936 0
Parent demographics using study specific questionnaire conducted by interview and review of medical records. Parent demographic data will include:
Maternal perinatal risk factors for cerebral palsy
Maternal obstetric history
Marital status
Maternal and paternal country of origin, level of education and languages spoken
Timepoint [24] 386936 0
Enrolment
Secondary outcome [25] 386937 0
Child socio-demographics using study specific questionnaire conducted by interview with parent or carer. Child socio-demographic data will include:
Child demographics include:
Caring arrangements of child, including formal care
Health and disability diagnoses
Participation in external research studies
Timepoint [25] 386937 0
12 & 24 months
Secondary outcome [26] 386938 0
Parent socio-demographics using study specific questionnaire conducted by interview with parent. Parent socio-demographic data will include:
Current level of education, age, occupation, marital status, household income, number of people living in household
Timepoint [26] 386938 0
12 & 24 months

Eligibility
Key inclusion criteria
1. Neuroimaging predictive of a motor disability
2. General Movements Assessment indicates high risk for cerebral palsy
3. Hammersmith Infant Neurological Examination scores indicate high risk for cerebral palsy
or 4. A unilateral brain injury predictive of cerebral palsy AND clinical signs of asymmetry
Minimum age
3 Months
Maximum age
12 Months
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Progressive or neurodegenerative disorder or genetic disorder not associated with cerebral palsy
2. Other disability diagnosis (e.g. Downs Syndrome) but no identified cerebral palsy

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
A database will be established for all data storage and data will be analysed using SPSS v. 23 (SPSS Inc.), STATA 14. Descriptive statistics will be used to examine the cohort for each assessment at all time periods and normality assumptions investigated. The presence of comorbidities will be analysed using weighted estimating equations and multilevel mixed-effects models will be used for longitudinal data. Correlations will be conducted using Pearson’s correlations for normal data, where assumptions are not met appropriate measures will be taken. Between group differences will be investigated using t tests or Mann Whitney U tests where appropriate. Logistic regression will be used for motor tests at 3-4 months of age on GMFCS 1 at 2 years of age. Rates will be investigated using Poisson or negative binomial regression for time based data.
The GMFM-66 data will be plotted by age in months for the entire cohort and sub-studies within the cohort. Based on previous studies, the rate of motor development is expected to vary greatly so individual variations will be assessed in individual motor development prognostic curves. Smoothing of the curves will use the LMS (lambda-mu-sigma) method.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
26/10/2018
Date of last participant enrolment
Anticipated
31/12/2021
Actual
Date of last data collection
Anticipated
31/12/2023
Actual
Sample size
Target
300
Accrual to date
52
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 14968 0
The Children's Hospital at Westmead - Westmead
Recruitment hospital [2] 14969 0
Westmead Hospital - Westmead
Recruitment hospital [3] 14970 0
Nepean Hospital - Kingswood
Recruitment hospital [4] 14971 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [5] 14972 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [6] 14973 0
Sydney Children's Hospital - Randwick
Recruitment hospital [7] 14974 0
Royal Hospital for Women - Randwick
Recruitment hospital [8] 14975 0
John Hunter Children's Hospital - New Lambton
Recruitment hospital [9] 14976 0
Campbelltown Hospital - Campbelltown
Recruitment hospital [10] 14977 0
St George Hospital - Kogarah
Recruitment hospital [11] 14978 0
Liverpool Hospital - Liverpool
Recruitment hospital [12] 14979 0
The Royal Women's Hospital - Parkville
Recruitment hospital [13] 14980 0
The Royal Childrens Hospital - Parkville
Recruitment hospital [14] 14981 0
Mercy Hospital for Women - Heidelberg
Recruitment hospital [15] 14982 0
Monash Children’s Hospital - Clayton
Recruitment hospital [16] 14983 0
Sunshine Hospital - St Albans
Recruitment hospital [17] 14984 0
The Northern Hospital - Epping
Recruitment hospital [18] 14985 0
Casey Hospital - Berwick
Recruitment hospital [19] 14986 0
Frankston Hospital - Frankston
Recruitment hospital [20] 14987 0
Lady Cilento Children's Hospital - South Brisbane
Recruitment hospital [21] 14988 0
Queensland Children's Hospital - South Brisbane
Recruitment hospital [22] 14989 0
Mater Mother's Hospital - South Brisbane
Recruitment hospital [23] 14990 0
Royal Brisbane & Womens Hospital - Herston
Recruitment hospital [24] 14991 0
Gold Coast University Hospital - Southport
Recruitment hospital [25] 14992 0
Sunshine Coast University Hospital - Birtinya
Recruitment hospital [26] 16690 0
Cerebral Palsy Alliance - Allambie Heights
Recruitment postcode(s) [1] 28258 0
2145 - Westmead
Recruitment postcode(s) [2] 28259 0
2747 - Kingswood
Recruitment postcode(s) [3] 28260 0
2065 - St Leonards
Recruitment postcode(s) [4] 28261 0
2050 - Camperdown
Recruitment postcode(s) [5] 28262 0
2031 - Randwick
Recruitment postcode(s) [6] 28263 0
2305 - New Lambton
Recruitment postcode(s) [7] 28264 0
2560 - Campbelltown
Recruitment postcode(s) [8] 28265 0
2217 - Kogarah
Recruitment postcode(s) [9] 28266 0
2170 - Liverpool
Recruitment postcode(s) [10] 28267 0
3052 - Parkville
Recruitment postcode(s) [11] 28268 0
3084 - Heidelberg
Recruitment postcode(s) [12] 28269 0
3168 - Clayton
Recruitment postcode(s) [13] 28270 0
3021 - St Albans
Recruitment postcode(s) [14] 28271 0
3076 - Epping
Recruitment postcode(s) [15] 28272 0
3806 - Berwick
Recruitment postcode(s) [16] 28273 0
3199 - Frankston
Recruitment postcode(s) [17] 28274 0
4101 - South Brisbane
Recruitment postcode(s) [18] 28275 0
4029 - Herston
Recruitment postcode(s) [19] 28276 0
4215 - Southport
Recruitment postcode(s) [20] 28277 0
4575 - Birtinya
Recruitment postcode(s) [21] 30288 0
2100 - Allambie Heights
Recruitment postcode(s) [22] 30289 0
2100 - Allambie

Funding & Sponsors
Funding source category [1] 304051 0
Government body
Name [1] 304051 0
NHMRC
Country [1] 304051 0
Australia
Funding source category [2] 304053 0
Charities/Societies/Foundations
Name [2] 304053 0
Cerebral Palsy Alliance Research Foundation
Country [2] 304053 0
Australia
Primary sponsor type
University
Name
University of Melbourne
Address
Alan Gilbert Building, 161 Barry Street, Parkville, VIC 3053
Country
Australia
Secondary sponsor category [1] 304244 0
None
Name [1] 304244 0
Address [1] 304244 0
Country [1] 304244 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304543 0
Sydney Children's Hospital Network
Ethics committee address [1] 304543 0
Corner Hawkesbury Road and Hainsworth Street, Locked Bag 4001, Westmead NSW 2145, Sydney Australia
Ethics committee country [1] 304543 0
Australia
Date submitted for ethics approval [1] 304543 0
30/07/2018
Approval date [1] 304543 0
04/10/2018
Ethics approval number [1] 304543 0
HREC/18/SCHN/322
Ethics committee name [2] 304545 0
Cerebral Palsy Alliance Ethics Committee
Ethics committee address [2] 304545 0
187 Allambie Road, Allambie Heights, NSW 2100
Ethics committee country [2] 304545 0
Australia
Date submitted for ethics approval [2] 304545 0
16/04/2018
Approval date [2] 304545 0
08/06/2018
Ethics approval number [2] 304545 0
2018_04_03

Summary
Brief summary
This study aims to describe the early natural history of cerebral palsy (CP) by mapping the development of infants with, or at-risk of CP, over the first two years of life. Infants will be assessed in their homes by a trained therapist at regular intervals up to 24 months of age, across a variety of developmental domains (such as movement, thinking skills, language, and more). This will provide, for the first time, comprehensive developmental trajectories of this group. This will contribute to the existing knowledge of CP development, which will assist clinicians and therapists in: 1) accurate diagnosis and prediction of CP, 2) providing targeted early interventions at the 'just-right' challenge, and 3) aiding in the early monitoring and prevention of secondary impairments (for example contracture and hip dislocation). Where indicated, individual participants' results from this study will be used to inform their therapy. A cost analysis of healthcare resources will also be applied as a part of the study. This study is intended to form part of a larger multi-site international study.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 97326 0
Dr Cathy Morgan
Address 97326 0
88 Mallett St, Cerebral Palsy Alliance Research Institute, The University of Sydney
Camperdown, NSW, 2050
Country 97326 0
Australia
Phone 97326 0
+61 408 205 542
Fax 97326 0
Email 97326 0
[email protected]
Contact person for public queries
Name 97327 0
Dr Cathy Morgan
Address 97327 0
88 Mallett St, Cerebral Palsy Alliance Research Institute, The University of Sydney
Camperdown, NSW, 2050
Country 97327 0
Australia
Phone 97327 0
+61 408 205 542
Fax 97327 0
Email 97327 0
[email protected]
Contact person for scientific queries
Name 97328 0
Dr Cathy Morgan
Address 97328 0
88 Mallett St, Cerebral Palsy Alliance Research Institute, The University of Sydney
Camperdown, NSW, 2050
Country 97328 0
Australia
Phone 97328 0
+61 408 205 542
Fax 97328 0
Email 97328 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 reported in collectively and anonymously.


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.