Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12607000326493
Ethics application status
Approved
Date submitted
13/06/2007
Date registered
19/06/2007
Date last updated
13/04/2012
Type of registration
Prospectively registered

Titles & IDs
Public title
A randomised controlled trial to determine the optimum frequency of Botulinum Toxin injections to the calf in children with cerebral palsy
Scientific title
A randomised controlled trial to determine the optimum frequency of Botulinum Toxin A injections to the calf in children with cerebral palsy
Secondary ID [1] 280296 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cerebral palsy in children 1875 0
Condition category
Condition code
Neurological 1969 1969 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Intervention group: Botulinum Toxin A calf muscle injections every 4 months over a 2 year period.

Dose: 6 U/kg per gastrocnemius in diplegia or per gastrocnemius and soleus in hemiplegia with 6 U/kg available for use elsewhere as clinically indicated. Total upper dose of 18 U/kg.
Intervention code [1] 1776 0
Treatment: Drugs
Comparator / control treatment
Active control group: Botulinum Toxin A calf muscle injections every 12 months over a 2 year period.
Control group
Active

Outcomes
Primary outcome [1] 2784 0
Passive length of gastrocnemius in degrees of dorsiflexion
Timepoint [1] 2784 0
At 0, 12 and 26 months
Secondary outcome [1] 4699 0
Level of Function measured using the Functional Mobility Scale
Timepoint [1] 4699 0
0, 12, 26 months
Secondary outcome [2] 4700 0
Quality of Life measured using the Child Health Questionnaire
Timepoint [2] 4700 0
0, 12, 26 months
Secondary outcome [3] 4701 0
Secondary Unresponsiveness to Botulinum Toxin A measured in two ways:
Assessing for the presence of neutralising antibodies to Botulinum Toxin A
Timepoint [3] 4701 0
Blood collected prior to botulinum Toxin injections and assessed every 6 months.
Secondary outcome [4] 4702 0
Assessing the amount of dynamic gastrocnemius shortness measured by gait analysis
Timepoint [4] 4702 0
Pre/post final injection at 26 and 27 months
Secondary outcome [5] 297052 0
3D ultrasound of medial gastrocnemius to determine muscle volumes
Timepoint [5] 297052 0
0, 12 and 26 months

Eligibility
Key inclusion criteria
Level I, II, or III on the Gross Motor Function Classification System for cerebral palsyGastrocnemius muscle length greater than 5 degrees with the knee extendedGastrocnemius spasticity (no heel contact during the stance phase of gait)
Minimum age
2 Years
Maximum age
5 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Previous Botulinum Toxin A injections to the calf musclePrevious calf surgeryContraindications to the use of Botulinum Toxin A such as known hypersensitivity to any ingredient in the formulation, presence of Myasthenia Gravis or Eaton Lambert syndrome, or the presence of infection at the proposed injection site(s).

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)
Allocation involves contacting the holder of the allocation schedule who is "off-site"
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The dynamic (adaptive) random allocation method of minimisation will be used with subjects categorised according to classification of cerebral palsy, severity of cerebral palsy and Botulinum toxin injections to muscles other than the calf.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Two groups are blinded in this study, the assessor assessing the outcomes and the data analyst analysing the results.
Phase
Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/07/2007
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
40
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 2109 0
Government body
Name [1] 2109 0
National Health and Medical Research Centre (NHMRC), Grant Number: 454705
Country [1] 2109 0
Australia
Primary sponsor type
Hospital
Name
The Royal Children's Hospital, Melbourne, Victoria
Address
Flemington Rd.
Parkville Victoria 3052
Country
Australia
Secondary sponsor category [1] 1916 0
Hospital
Name [1] 1916 0
Monash Medical Centre Southern Health
Address [1] 1916 0
Monash Medical Centre
246 Clayton Road
Clayton, Victoria 3168
Country [1] 1916 0
Australia
Secondary sponsor category [2] 1917 0
Other
Name [2] 1917 0
Murdoch Children's Research Institute
Address [2] 1917 0
Royal Children's Hospital
Flemington Rd.
Parkville Victoria 3052
Country [2] 1917 0
Australia
Secondary sponsor category [3] 1918 0
University
Name [3] 1918 0
Dept of Paediatrics University of Melbourne, Victoria
Address [3] 1918 0
Royal Children's Hospital
Flemington Rd.
Parkville Victoria 3052
Country [3] 1918 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 287078 0
Royal Children's Hospital Human Research Ethics Committee
Ethics committee address [1] 287078 0
Royal Children's Hospital
Flemington Rd,
Parkville Victoria 3052
Ethics committee country [1] 287078 0
Australia
Date submitted for ethics approval [1] 287078 0
Approval date [1] 287078 0
09/11/2007
Ethics approval number [1] 287078 0
27062A
Ethics committee name [2] 287079 0
Southern Health Research Directorate
Ethics committee address [2] 287079 0
Level 4, Main Block,
Monash Medical Centre
246 Clayton Road
Clayton, Victoria 3168
Ethics committee country [2] 287079 0
Australia
Date submitted for ethics approval [2] 287079 0
Approval date [2] 287079 0
29/08/2007
Ethics approval number [2] 287079 0
07083C

Summary
Brief summary
Cerebral Palsy (CP) is a disorder affecting around 2 in 1000 live births. Commonly, children with CP have spasticity in their muscles causing stiffness. When Botox (Botulinum Toxin A) is injected into a spastic muscle, it helps it to relax for around 3 months, after which the effect begins to wear off. During this relaxed time, the muscle is able to exercise through a greater range, helping to prevent contractures from forming.

Botox is therefore used to both reduce spasticity in the short term, and to slow or prevent the development of contractures in the long term. This in turn, assists to delay corrective orthopaedic surgery until the later childhood years when surgical outcomes are more predictable and longer lasting.

Currently, the most important clinical question is how often Botox should be used. More regular injections may provide additional time that the effects of Botox are working, and muscle contractures could be delayed more effectively.

The aim of this study is to compare over a two-year period, the effects of Botox injections once a year compared to 3 times a year (every four months). The main measure will be the rate of development of contractures over the two years. Measurements (such as calf strength, questionnaires and blood tests) will also be made to determine whether either program negatively affects the muscle, whether the children in either group have a different level of function or quality of life and whether either program leads to the Botox having a reduced effect over time.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 27879 0
Address 27879 0
Country 27879 0
Phone 27879 0
Fax 27879 0
Email 27879 0
Contact person for public queries
Name 10965 0
Tandy Hastings-Ison
Address 10965 0
Hugh Williamson Gait Analysis Laboratory
The Royal Children's Hospital
Flemington Rd
Parkville VIC 3052
Country 10965 0
Australia
Phone 10965 0
+61 3 93455354
Fax 10965 0
+61 3 93455447
Email 10965 0
[email protected]
Contact person for scientific queries
Name 1893 0
Professor Kerr Graham
Address 1893 0
Department of Orthopaedics
The Royal Children's Hospital
Flemington Rd
Parkville VIC 3052
Country 1893 0
Australia
Phone 1893 0
+61 3 93455399
Fax 1893 0
+61 3 93455447
Email 1893 0
[email protected]

No information has been provided regarding IPD availability


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
SourceTitleYear of PublicationDOI
EmbaseInjection frequency of botulinum toxin A for spastic equinus: a randomized clinical trial.2016https://dx.doi.org/10.1111/dmcn.12962
N.B. These documents automatically identified may not have been verified by the study sponsor.