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Trial registered on ANZCTR


Registration number
ACTRN12609000034235
Ethics application status
Approved
Date submitted
9/12/2008
Date registered
19/01/2009
Date last updated
19/01/2009
Type of registration
Prospectively registered

Titles & IDs
Public title
A randomised clinical trial to determine the relative benefits of botulinum toxin injections, ankle foot orthosis or a combination of both on knee hyperextension during walking in people with chronic stroke.
Scientific title
For people with stroke, does botulinum toxin or ankle foot orthosis provide better control of knee hyperextension in the stance phase of gait?
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Knee hyperextension in stance 4098 0
People with stroke 4099 0
Condition category
Condition code
Stroke 4294 4294 0 0
Haemorrhagic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
There are 3 proposed interventions: Botulinum toxin alone, botulinum toxin with ankle foot orthosis, and ankle foot orthosis with normal saline.
Botulinum toxin A (BoNT-A) is a neuromuscular blocking agent. When injected it produces a localised partial but reversible chemical denervation of the muscle, resulting in localised muscle paralysis. This effect is temporary. The ankle foot orthosis (AFO) to be used is a rigid moulded splint that goes around the ankle and comes up the front of the shin and over the top of the knee cap. The splint is used to control the foot position and cause pressure at the knee to realign it. There is reinforcement at the ankle to strengthen the splint.
Participants will be randomised to one of three intervention groups (5 people in each group.) All participants will attend a clinic within Southern Health and receive a single dose intra-muscular injection of either 200U BoNT-A or normal saline (100 ml of 9% sodium chloride) - 10 people will receive BoNT-A and 5 people will receive normal saline. The injections will be given by a medical specialist experienced in the use of intra-muscular BoNT-A. The 10 persons receiving an AFO will attend an orthotist for casting and fitting of the AFO (2-3 x visits required) prior to injection. They will commence wearing the AFO the day following the injection. The participants will be instructed to gradually wear in the AFO. It is usual to start with wearing the splint for one or two hours on the first day. Each consecutive day one hour or wear is added (first day of wear for 2 hours, second day of wear for 3 hours, third day of wear for 4 hours etc.) After two weeks the AFO should be able to be worn full time. Participants will be instructed to continue wearing the splint daily until all assessments have been completed (at least 12 weeks).
Following injection all participants will receive 6 weeks of twice weekly gait re-education conducted by physiotherapists experienced in the management of stroke.
Intervention code [1] 3808 0
Treatment: Drugs
Intervention code [2] 3809 0
Treatment: Devices
Comparator / control treatment
Normal saline (9% sodium chloride) will be administered to 5 participants rendomly allocated to the non-BoNT-A group. Neither the participants nor the therapists will be aware of who has not received BoNT-A. The normal saline will be administered as a once-only intra-muscular injection following receipt of the AFO, and prior to attendance at gait re-education.
Control group
Active

Outcomes
Primary outcome [1] 5179 0
Decreased knee hyperextension in the stance phase of gait, which will be determined by an improvement of 5 or more degrees on the joint kinematics. Joint kinematics (range of motion) during walking are routinely collected using thre-dimensional (3D) gait anlaysis. The procedure is as follows: A lower-body set of reflective markers will be placed on the skin of participants at specific locations. The participants will be asked to complete a number of walks along a 10 metre walkway in bare feet, and again with their shoes and AFO. Their walking will be recorded using an 8 camera 3-D system (Vicon). Advanced modeling software will be used to calculate the kinematics (joint angles) and kinetics (joint moments and powers) of the pelvis, hips, knees and ankles. A musculo-skeletal examination by an experienced physiotherapist including passive and dynamic range of motion are included as a routine part of a clinical 3D gait analysis.
Timepoint [1] 5179 0
Baseline data will be collected prior to the participants being allocated to a treatment group. All participants will have repeat assessments completed at 6 weeks and 12 weeks following injection.
Primary outcome [2] 5180 0
Increased ankle range of motion will be decided by an improvement of 5 or more degrees in dynamic range of ankle dorsiflexion on examination; and of 5 or more degrees of improvement in dorsiflexion during gait, at initial contact and in mid-stance. Musculo-skeletal examination of range of motion is routinely carried out prior to collection of 3-D data collection, which is used to provide range of motion during walking. Data collection for 3D gait analysis has previously been described (see primary outcome 1).
Timepoint [2] 5180 0
Baseline data will be collected prior to the participants being allocated to a treatment group. All participants will have repeat assessments completed at 6 weeks and 12 weeks following injection.
Secondary outcome [1] 8724 0
Improved overall kinematics and kinetics, improved average spatio-temporal data and changes in passive and dynamic range of motion will be calculated from the 3-D gait analysis and the accompanying physical examinations. The method for collection of these measures is already desribed in the primary outcomes.
Timepoint [1] 8724 0
Baseline data will be collected prior to the participants being allocated to a treatment group. All participants will have repeat assessments completed at 6 weeks and 12 weeks following injection.

Eligibility
Key inclusion criteria
People with stroke affecting one side of the body;
Passive dorsiflexion less than plantigrade;
dynamic range of gastrocnemius greater than 15 degrees;
knee hyperextension more than 0 degrees in mid-stance;
able to walk more than 400 metres without assistance;
agree to injections +/- ankle foot orthosis
agree to repeat assessments.
Minimum age
18 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Participants will have no other neurological, cardiothoracic, orthopaedic or psychological condition affecting walking ability. Other exclusion criteria include: incompetence to provide informed consent; known contraindications to botulinum toxin, including sensitivity, infection and pregancy; participants who have received BoNT-A or phenol injections for the treatment of increased tone within the previous 6 months.

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)
Rehabilitation and community centres in the South-East suburbs of Melbourne will be asked to refer possible suitable participants for gait analysis. Patients referred for clinical gait analysis who meet the inclusion criteria will be asked to participate in the study. The person(s) determining eligibility for inclusion in the trial will be unaware athe the time of decision making, to which group the subject will be allocated. Randomisation of the participants into treatment groups will be conducted by a separate department, and allocation will involve contacting that department with the participant details. Neither the prospective participant nor the principal researchers will be aware to which group the participant will be allocated. Participants meeting the inclusion criteria and consenting to participate will be allocated to one of three intervention groups, which will be administered by the pharmacy department who will be supplying the BoNT-A and normal saline. Participants will be asked to attend the Kingston centre for injection of either botulinum toxin or saline. If allocated to an orthotic intervention, they will be cast for, and receive, the ankle foot orthosis prior to injection. Throughout the study the participants and the assessors will remain blinded to the drug intervention; AFO use will obviously be known to participants post-allocation, and to assessors who are involved with the re-assessment.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The randomisation process will be administered by the Kingston Centre pharmacy department, using a computer generated allocation system.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/02/2009
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
15
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 4264 0
Commercial sector/Industry
Name [1] 4264 0
Allergan Australia
Country [1] 4264 0
Australia
Funding source category [2] 4265 0
Charities/Societies/Foundations
Name [2] 4265 0
John Cockayne Memorial Aged Care Research Fund
Country [2] 4265 0
Australia
Primary sponsor type
Hospital
Name
Clinical Gait Analysis Service
Address
Kingston Centre,
Corner Kingston Road and Warrigal Road,
Cheltenham,
Victoria 3192
Country
Australia
Secondary sponsor category [1] 3836 0
Hospital
Name [1] 3836 0
Kingston Centre
Address [1] 3836 0
Corner Kingston Road and Warrigal Road,
Cheltenham,
Victoria 3192
Country [1] 3836 0
Australia
Other collaborator category [1] 501 0
Commercial sector/Industry
Name [1] 501 0
Orthopaedic Appliances Pty Ltd
Address [1] 501 0
281 Clayton Road,
Clayton,
Victoria 3168
Country [1] 501 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 6316 0
Southern Health Human Research Ethics Committee
Ethics committee address [1] 6316 0
Research Directorate, Level 4,
Main Block,
Monash Medical Centre,
246 Clayton Road,
Clayton
Victoria 3168
Ethics committee country [1] 6316 0
Australia
Date submitted for ethics approval [1] 6316 0
01/06/2008
Approval date [1] 6316 0
10/11/2008
Ethics approval number [1] 6316 0
08042B

Summary
Brief summary
This is a pilot study to investigate the effects of Botulinum toxin (BoNT-A) and ankle foot orthosis (AFO) on controlling knee hyperextension during walking, in people who have had a stroke. It is hypothesised that a combination of BoNT-A and AFO will result in 5 degrees or more decrease in knee hyperextension, and improved ankle dorsiflexion, during walking, than BoNT-A or AFO alone. It is also hyptohesised that a combination of BoNT-A and AFO will increase walking speed by 10cm/sec or more, than either BoNT-A or AFO alone. The results of this study will provide information to calculate power and sample size requirements for a more comprehensive study.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 35020 0
Address 35020 0
Country 35020 0
Phone 35020 0
Fax 35020 0
Email 35020 0
Contact person for public queries
Name 12367 0
Dr. Anna Murphy
Address 12367 0
Manager,
Clinical Gait Analysis Service,
Kingston Centre,
Corner Kingston Road and Warrigal Road,
Cheltenham
Victoria 3192
Country 12367 0
Australia
Phone 12367 0
+61 3 92651453
Fax 12367 0
+61 3 92651577
Email 12367 0
[email protected]
Contact person for scientific queries
Name 3295 0
Dr. Anna Murphy
Address 3295 0
Manager,
Clinical Gait Analysis Service,
Kingston Centre,
Corner Kingston Road and Warrigal Road,
Cheltenham
Victoria 3192
Country 3295 0
Australia
Phone 3295 0
+61 3 92651453
Fax 3295 0
+61 3 92651577
Email 3295 0
[email protected]

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No Supporting Document Provided



Results publications and other study-related documents

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