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Trial registered on ANZCTR


Registration number
ACTRN12622000788774p
Ethics application status
Not yet submitted
Date submitted
11/05/2022
Date registered
2/06/2022
Date last updated
2/06/2022
Date data sharing statement initially provided
2/06/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Australian Cerebral Palsy Musculoskeletal Health Network: assessment of hip, spine and fracture complications in children with Cerebral Palsy.
Scientific title
Australian Cerebral Palsy Musculoskeletal Health Network: Longitudinal cohort study to evaluate hip displacement, scoliosis and skeletal fragility in children with cerebral palsy Gross Motor Function Classification System (GMFCS) III-V
Secondary ID [1] 306969 0
Nil known
Universal Trial Number (UTN)
U1111-1278-1702
Trial acronym
CPMSK
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cerebral Palsy 326084 0
Scoliosis 326085 0
Hip displacement 326086 0
Osteoporosis 326087 0
Condition category
Condition code
Neurological 323396 323396 0 0
Other neurological disorders
Musculoskeletal 323397 323397 0 0
Other muscular and skeletal disorders
Musculoskeletal 323398 323398 0 0
Osteoporosis

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Prospective cohort study (n=500, Gross Motor Function Classification System (GMFCS) III-V, aged 4-8 years) for 4 years longitudinal evaluation of hip, spine and skeletal fragility onset, progression, biomarkers and risk factors for outcomes at 8-12 years;
Annual Pelvic x-ray, anterior-posterior (AP) spine x-ray, duel energy x-ray absorptiometry (DXA), peripheral quantitative computer tomography (pQCT)- Delivered by paediatric radiographer, nuclear medicine technician or clinical researcher accredited to perform DXA and pQCT. It is anticipated that these assessments will take a total of 2 hours to perform. Undertaken annually for 4 years of the study.
Annual questionnaires completed by parents and participants: Child Health Utility instrument (CHU9D), CPCHILD - delivered by clinical researchers. It is anticipated that it will take up to 60 minutes to complete these questionnaires. Undertaken annually for 4 years of the study.
Physical activity: ActiGraph GT3X+ for 7 consecutive days Annual. Delivered by exercise physiologists. This is not a physical activity intervention, but rather a measure of physical activity that the child undertakes spontaneously. Undertaken annually for 4 years of the study.
Blood tests: Calcium, Magnesium, Phosphate, (CMP) 25 Hydroxy vitamin D (25OHD). Annual. Blood collected by paediatric phlebotomist. A numbing cream will be applied prior to the collection of blood. It is anticipated blood collection will take 5 minutes. Undertaken annually for 4 years of the study.
Intervention code [1] 323420 0
Early Detection / Screening
Intervention code [2] 323421 0
Diagnosis / Prognosis
Comparator / control treatment
Published reference data for DXA and pQCT be comparing the results of your study with the aggregated results in these published papers
DXA:
1. Lu PW, Briody JN, Ogle GD, et al. Bone mineral density of total body, spine, and
femoral neck in children and young adults: a cross-sectional and longitudinal
study. J Bone Miner Res 1994;9:1451–8.
2. Ogle GD, Allen JR, Humphries IR, et al. Body-composition assessment by dual energy
x-ray absorptiometry in subjects aged 4–26 y. Am J Clin Nutr 1995;61:
746–53.
3. Hogler W, Briody J, Woodhead HJ, et al. Importance of lean mass in the
interpretation of total body densitometry in children and adolescents. J Pediatr
2003;143:81–8.
pQCT:
1. Rauch F, Schoenau E. Peripheral quantitative computed
tomography of the distal radius in young subjects – New
reference data and interpretation of results. Journal of
Musculoskeletal and Neuronal Interactions 2005;5(2):
119–126.
2. Moyer-Mileur LJ, Quick JL, Murray MA. Peripheral quantitative
computed tomography of the tibia: Pediatric reference
values. Journal of Clinical Densitometry 2008;11(2):
283–294.

Published data on functional status:
1. Jackman, M., Sakzewski, L., Morgan, C., Boyd, R.N., Brennan, S.E., Langdon, K., Toovey, R.A.M., Greaves, S., Thorley, M. and Novak, I. (2022), Interventions to improve physical function for children and young people with cerebral palsy: international clinical practice guideline. Dev Med Child Neurol, 64: 536-549
Control group
Historical

Outcomes
Primary outcome [1] 331150 0
Hip radiological measure from anterior-posterior (AP) pelvis x-ray. Migration percentage (MP) is the gold standard of femoral head displacement.
Timepoint [1] 331150 0
Assessed annually for 4 years post-enrolment
Primary outcome [2] 331151 0
Hip radiological measure from AP pelvis x-ray. Acetabular index (AI), assesses acetabular dysplasia.
Timepoint [2] 331151 0
Measured annually with final measurement at 4 years post-enrolment
Primary outcome [3] 331152 0
Hip radiological measure from AP pelvis x-ray. Hilgreneiner’s Epiphyseal Angle (HEA) and femoral neck-shaft angle (NSA) describe the proximal femoral epiphysis and with cerebral palsy surveillance program (CPUP) score offer prognosis for bony surgery.
Timepoint [3] 331152 0
Measured annually with final measurement at 4 years post-enrolment
Secondary outcome [1] 409058 0
Primary outcome:
Hip: Dual energy x-ray absorptiometry (DXA), age/height matched areal bone mineral density (aBMD; g/cm2), bone mineral content (BMC; grams)
Timepoint [1] 409058 0
Measured annually with final measurement at 4 years post-enrolment
Secondary outcome [2] 409059 0
Primary outcome:
Lumbar spine: Dual energy x-ray absorptiometry (DXA), age/height matched areal bone mineral density (aBMD; g/cm2), bone mineral content (BMC; grams)
Timepoint [2] 409059 0
Measured annually with final measurement at 4 years post-enrolment
Secondary outcome [3] 409061 0
Primary outcome:
Total body: Dual energy x-ray absorptiometry (DXA), age/height matched areal bone mineral density (aBMD; g/cm2), bone mineral content (BMC; grams)
Timepoint [3] 409061 0
Measured annually with final measurement at 4 years post-enrolment
Secondary outcome [4] 409062 0
Primary outcome:
Lateral distal femur: Dual energy x-ray absorptiometry (DXA), age/height matched areal bone mineral density (aBMD; g/cm2), bone mineral content (BMC; grams)
Timepoint [4] 409062 0
Measured annually with final measurement at 4 years post-enrolment
Secondary outcome [5] 409064 0
Primary outcome:
Posterior-Anterior (PA) spine radiograph. Measured by two investigators following intra-observer calculations.
Major/compensatory structural curve (Cobb)
Timepoint [5] 409064 0
Measured annually with final measurement at 4 years post-enrolment
Secondary outcome [6] 409065 0
Primary Outcome:
Posterior-Anterior (PA) spine radiograph. Measured by two investigators following intra-observer calculations.
Thoracic kyphosis angle
Timepoint [6] 409065 0
Measured annually with final measurement at 4 years post-enrolment
Secondary outcome [7] 409066 0
Parent Reported Secondary outcomes: CHU9D is a generic instrument for children aged 7-11 gives preference-based utility index for economic evaluations
Timepoint [7] 409066 0
Measured annually with final measurement at 4 years post-enrolment
Secondary outcome [8] 409067 0
Primary outcome:
Posterior-Anterior (PA) spine radiograph. Measured by two investigators following intra-observer calculations.
Rotational spinal deformity
Timepoint [8] 409067 0
Measured annually with final measurement at 4 years post-enrolment
Secondary outcome [9] 409068 0
Posterior-Anterior (PA) spine radiograph. Measured by two investigators following intra-observer calculations.
Sagittal balance (sagittal vertical axis)
Timepoint [9] 409068 0
Measured annually with final measurement at 4 years post-enrolment
Secondary outcome [10] 409069 0
Posterior-Anterior (PA) spine radiograph. Measured by two investigators following intra-observer calculations.
Sacral shift (central sacral vertical line)
Timepoint [10] 409069 0
Measured annually with final measurement at 4 years post-enrolment
Secondary outcome [11] 409070 0
Posterior-Anterior (PA) spine radiograph. Measured by two investigators following intra-observer calculations.
Shoulder asymmetry (vertical height acromion)
Timepoint [11] 409070 0
Measured annually with final measurement at 4 years post-enrolment
Secondary outcome [12] 409071 0
Posterior-Anterior (PA) spine radiograph. Measured by two investigators following intra-observer calculations.
Spinal deformity severity by CPUP
Timepoint [12] 409071 0
Measured annually with final measurement at 4 years post-enrolment
Secondary outcome [13] 409846 0
Rib hump (Adams Forward Bend Test). Evaluated by trained physiotherapist
Timepoint [13] 409846 0
Measured annually with final measurement at 4 years post-enrolment
Secondary outcome [14] 409847 0
Lateral spine flexibility test (in lying/sit), Outcome: distance (cm) finger-feet left and right. Evaluated by trained physiotherapist
Timepoint [14] 409847 0
Measured annually with final measurement at 4 years post-enrolment
Secondary outcome [15] 409848 0
Functional reach test left and right in sitting/stand. Evaluated by trained physiotherapist
Timepoint [15] 409848 0
Measured annually with final measurement at 4 years post-enrolment
Secondary outcome [16] 409849 0
Musculoskeletal Examination Surveillance in Europe and Australian Spasticity Assessment Scales.
Lower limb muscle length/contracture
Timepoint [16] 409849 0
Measured annually with final measurement at 4 years post-enrolment
Secondary outcome [17] 409850 0
Musculoskeletal Examination Surveillance in Europe and Australian Spasticity Assessment Scales.
Range of motion
Timepoint [17] 409850 0
Measured annually with final measurement at 4 years post-enrolment
Secondary outcome [18] 409851 0
Motor type/distribution using Musculoskeletal Examination Surveillance in Europe and Australian Spasticity Assessment Scales.
Timepoint [18] 409851 0
Measured annually with final measurement at 4 years post-enrolment
Secondary outcome [19] 409852 0
Peripheral quantitative computer tomography (pQCT) of tibia in GMFCS III and subset of GMFCS IV:
Volumetric bone mineral density (BMD) of cortical bone (65% site)
Timepoint [19] 409852 0
Measured 2nd yearly with final measurement at 4 years post-enrolment
Secondary outcome [20] 409853 0
Peripheral quantitative computer tomography (pQCT) of tibia in GMFCS III and subset of GMFCS IV:
Volumetric BMD of trabecular bone (4% site)
Timepoint [20] 409853 0
Measured 2nd yearly with final measurement at 4 years post-enrolment
Secondary outcome [21] 409854 0
Peripheral quantitative computer tomography (pQCT) of tibia in GMFCS III and subset of GMFCS IV:
65% site cortical size
Timepoint [21] 409854 0
Measured 2nd yearly with final measurement at 4 years post-enrolment
Secondary outcome [22] 409855 0
Peripheral quantitative computer tomography (pQCT) of tibia in GMFCS III and subset of GMFCS IV:
65% Strength Strain Index (SSI)
Timepoint [22] 409855 0
Measured 2nd yearly with final measurement at 4 years post-enrolments
Secondary outcome [23] 409856 0
Fracture rate: Fractures using radiological evidence. Parents will report occurrence <24 hours, bring X-ray films and management details. Annual fracture questionnaire will record fracture history will be developed specifically for this study
Timepoint [23] 409856 0
Measured 2nd yearly with final measurement at 4 years post-enrolment
Secondary outcome [24] 409857 0
Habitual Physical Activity: will be measured using triaxial accelerometers worn on the less-affected wrist (ActiGraph GT3X+) and less-affected thigh (Axivity AX3) for 7 days during free living. Raw accelerometer signal will be processed into HPA outcomes using CI Trost’s machine-learned PA classification algorithms specifically trained and validated for youth with CP who are ambulatory or use mobility aids for ambulation. The algorithms use statistical and frequency domain features in the raw acceleration signal to identify activity type and quantify time spent in sedentary activities (sitting or lying down, transfers); wheelchair propulsion, standing, walking, and cycling.
Timepoint [24] 409857 0
Measured annually with final measurement at 4 years post-enrolment
Secondary outcome [25] 409858 0
Growth and nutritional status: Body Mass (kg) using chair scales.
Timepoint [25] 409858 0
Measured annually with final measurement at 4 years post-enrolment
Secondary outcome [26] 409859 0
Growth and nutritional status:
Height (cm) with a stadiometer, or length using a supine measuring board, Knee height and upper-arm length to predict height.
Timepoint [26] 409859 0
Measured annually with final measurement at 4 years post-enrolment
Secondary outcome [27] 409860 0
Growth and nutritional status:
Body mass index as per Cerebral Palsy (CP) growth protocol.
Calculated using Mass using chair scales and Height with a stadiometer, or length using a supine measuring board.
Timepoint [27] 409860 0
Measured annually with final measurement at 4 years post-enrolment
Secondary outcome [28] 409861 0
Body composition: DXA measurements of fat mass
Timepoint [28] 409861 0
Measured 2nd yearly with final measurement at 4 years post-enrolment
Secondary outcome [29] 409862 0
Body composition: DXA measurements of fat free mass
Timepoint [29] 409862 0
Measured 2nd yearly with final measurement at 4 years post-enrolment
Secondary outcome [30] 409863 0
DXA measurements of bone mineral content (BMC).
Timepoint [30] 409863 0
Measured 2nd yearly with final measurement at 4 years post-enrolment
Secondary outcome [31] 409864 0
Dietary energy intakes through our validated food records.
Timepoint [31] 409864 0
Measured annually with final measurement at 4 years post-enrolment
Secondary outcome [32] 409865 0
Feeding through our parent report questionnaire.
Timepoint [32] 409865 0
Measured annually with final measurement at 4 years post-enrolment
Secondary outcome [33] 409866 0
Pain: Pediatric Pain Profile collects data on episodes of pain, treatment, physician contacts, medication use.
Timepoint [33] 409866 0
Measured annually with final measurement at 4 years post-enrolment
Secondary outcome [34] 409867 0
Blood collected by phlebotomists or under GA (during procedures), for 25-hydroxy vitamin D,
Timepoint [34] 409867 0
Measured annually with final measurement at 4 years post-enrolment
Secondary outcome [35] 409868 0
Blood collected by phlebotomists or under GA (during procedures), for calcium
Timepoint [35] 409868 0
Measured annually with final measurement at 4 years post-enrolment
Secondary outcome [36] 409869 0
Blood collected by phlebotomists or under GA (during procedures), for iron,
Timepoint [36] 409869 0
Measured annually with final measurement at 4 years post-enrolment
Secondary outcome [37] 409870 0
Parent Reported Secondary outcomes: The Caregiver Priorities & Child Health Index of Life with Disabilities (CPCHILD©) Q has 6 domains: ADL; Positioning, Transferring & Mobility; Comfort/Emotions; Communication/Social; Health; and QOL, distinguishes between GMFCS.
Timepoint [37] 409870 0
Measured annually with final measurement at 4 years post-enrolment
Secondary outcome [38] 409871 0
Sexual Maturation: Legal guardians complete standardised Tanner stage puberty diagrams to evaluate the child’s pubertal stage. Data will be reviewed by a physician for precocious puberty
Timepoint [38] 409871 0
Measured annually with final measurement at 4 years post-enrolment
Secondary outcome [39] 409872 0
Two separate outcomes measurers of a validated parent reported food frequency questionnaire, including gastrostomy feeds and Sun Exposure: Diary to measure daily UV performed during 7 day physical activity, within 2 weeks 25OHD levels.
Timepoint [39] 409872 0
Measured annually with final measurement at 4 years post-enrolment
Secondary outcome [40] 409873 0
Economic Evaluation: A better understanding of the value and costs of a national approach would lead to better decision-making regarding hip, spine, and bone fragility complications in CP. We will perform an economic evaluation of surveillance/prevention programs for MSK problems in CP. A cost-consequence analysis (CCA) will be undertaken from the societal perspective to attain Aims 3 and 4. CCA provides a summary of varied health, non-health costs and multi-dimensional outcomes, is simple to understand and apply by decision-makers. CCA will capture direct medical costs (drug, physician visits, hospital stays, and home care), and direct non-medical costs (e.g. devices, transportation, and paid caregiver time). Resource use data and direct costs of treatments will be collected through Health Resource Use (HRU) Q supplemented by MBS and PBS data. HRU includes data on screening, therapy frequency/duration, hospital admissions, medical visits, operations, medications, equipment, and parent time for appointments. Standard cost sources (MBS, PBS, hospital, DRGs for IP/OP services) will be applied to resource use and total cost of care calculated per child aged 2-12 years. CCA will report health outcomes to demonstrate value for money, including best possible musculoskeletal health, physical function, greater QOL, non-health effects, and non-patient effects (carer wellbeing and QOL). CCA will report costs and outcomes in a simple and disaggregated format to help policymakers better understand the effects of prevention programs for MSK problems in CP across costs and outcomes. The analysis will be performed on a 4-years’ time horizon, with a 3% discount rate to account for time preference.
Timepoint [40] 409873 0
Final measurement at 4 years post-enrolment

Eligibility
Key inclusion criteria
Prospective Study: Children aged 4-8 years with Cerebral Palsy GMFCS III-V
Minimum age
4 Years
Maximum age
8 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Unable or unwilling to undertake annual review for 4 years

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
Sample size and power: The total number of participants with data for the primary outcome (MP – Aim 1) is expected to be n=450 (assume 4- yr data from 90% of 500 enrolled participants based on attrition in previous NHMRC funded cohorts run by this team. If we assume approximately 70% of the cohort will have HD, then we will have 90% power (alpha=0.05) to detect differences between binary risk factor categories of 12% or greater, this is equivalent to identifying relative risks (RRs) of <0.80 or >1.18. Even when risk factors are unbalanced in a 4:1 ratio we will be able to identify RRs of <0.65 or >1.30. For Sc, if we assume overall cumulative incidence of 25%, we will be able to detect absolute between-group differences of >11%. Note that this is an underestimate of power due to the repeated annual measurements for each child.
Statistical analyses: CI Ware (Prof Biostatistics). To identify relationships between early biomarkers, early brain structure and clinical characteristics and bone quality with MSK complications we will build multivariable regression models according to our model. Association between risk factors and primary outcomes measured on the interval scale (eg MP%) will be investigated using mixed-effects linear regression models with child included as a random effect to account for repeated measures. Risk factor and time will be included as fixed effects, with an interaction term. Potentially confounding variables will be included. For binary outcomes mixed-effect logistic regression models will be constructed and mixed-effects Poisson models for count outcomes. When constructing predictive models, first important variables will be examined individually before the final multivariable model is selected using Bayesian Information Criteria. Model calibration will be tested graphically, and internal validation will use bootstrap resampling. Missing data will be treated case-by-case, 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 for each separate analysis mindful of type I & II error rates, as is standard practice.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
2/01/2023
Actual
Date of last participant enrolment
Anticipated
31/12/2024
Actual
Date of last data collection
Anticipated
31/12/2027
Actual
Sample size
Target
500
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,WA,VIC
Recruitment hospital [1] 22237 0
Queensland Children's Hospital - South Brisbane
Recruitment hospital [2] 22238 0
The Royal Childrens Hospital - Parkville
Recruitment hospital [3] 22239 0
Perth Children's Hospital - Nedlands
Recruitment hospital [4] 22240 0
John Hunter Children's Hospital - New Lambton
Recruitment hospital [5] 22241 0
Monash Children’s Hospital - Clayton
Recruitment hospital [6] 22242 0
Sydney Children's Hospital - Randwick
Recruitment hospital [7] 22243 0
The Children's Hospital at Westmead - Westmead
Recruitment postcode(s) [1] 37399 0
4101 - South Brisbane
Recruitment postcode(s) [2] 37400 0
3052 - Parkville
Recruitment postcode(s) [3] 37401 0
6009 - Nedlands
Recruitment postcode(s) [4] 37402 0
2305 - New Lambton
Recruitment postcode(s) [5] 37403 0
3168 - Clayton
Recruitment postcode(s) [6] 37404 0
2031 - Randwick
Recruitment postcode(s) [7] 37405 0
2145 - Westmead

Funding & Sponsors
Funding source category [1] 311282 0
Government body
Name [1] 311282 0
Australian Government Department of Health (Medical Research Future Fund)
Country [1] 311282 0
Australia
Primary sponsor type
University
Name
The University of Queensland
Address
St Lucia
Brisbane QLD 4072 Australia
Country
Australia
Secondary sponsor category [1] 312643 0
None
Name [1] 312643 0
N/A
Address [1] 312643 0
N/A
Country [1] 312643 0

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 310789 0
The University of Queensland
Ethics committee address [1] 310789 0
Ethics committee country [1] 310789 0
Australia
Date submitted for ethics approval [1] 310789 0
06/06/2022
Approval date [1] 310789 0
Ethics approval number [1] 310789 0
Ethics committee name [2] 310807 0
Children's Health Queensland
Ethics committee address [2] 310807 0
Ethics committee country [2] 310807 0
Australia
Date submitted for ethics approval [2] 310807 0
01/06/2022
Approval date [2] 310807 0
Ethics approval number [2] 310807 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 118870 0
Prof Craig Munns
Address 118870 0
Centre for Children’s Health Research (CCHR)
Room 603, UQ Child Health Research Centre
62 Graham Street
South Brisbane Qld 4101
Country 118870 0
Australia
Phone 118870 0
+61 7 3069 7362
Fax 118870 0
Email 118870 0
[email protected]
Contact person for public queries
Name 118871 0
Craig Munns
Address 118871 0
Centre for Children’s Health Research (CCHR)
Room 603, UQ Child Health Research Centre
62 Graham Street
South Brisbane Qld 4101
Country 118871 0
Australia
Phone 118871 0
+61 7 3069 7362
Fax 118871 0
Email 118871 0
[email protected]
Contact person for scientific queries
Name 118872 0
Craig Munns
Address 118872 0
Centre for Children’s Health Research (CCHR)
Room 603, UQ Child Health Research Centre
62 Graham Street
South Brisbane Qld 4101
Country 118872 0
Australia
Phone 118872 0
+61 7 3069 7362
Fax 118872 0
Email 118872 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


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
15863Study protocol  [email protected] Contacting the PI
15864Ethical approval  [email protected]



Results publications and other study-related documents

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