None listed
Conditions
Brief summary
Botulinum toxin type-A (BoNT-A) is a current standard treatment used to reduce muscle spasticity in children with cerebral palsy (CP). Intramuscular BoNT-A treatment results in temporary chemo-denervation of the injected muscle creating a muscle that is “weakened” for 2-5 months. Clinical trials in ambulant children with spastic type CP to date indicate that intramuscular BoNT-A injections to the calf muscles reduce spasticity and have a moderate influence in improving gait. In the long term, there is some evidence that BoNT-A injection may delay and reduce the requirement for surgery to treat musculoskeletal deformities and, provide modest functional benefits, however BoNT-A does not seem to prevent the development of muscle contracture. Studies of BoNT-A in animal models have shown reduced spasticity and muscle length maintenance however these adaptations occurred with a concomitant deterioration in muscle volume and strength. In humans significant atrophy in muscles of two healthy volunteers as well as a one child with spastic type CP has been reported. Recently, in older children with spastic type CP (not naive to BoNT-A), it was found that the volume of the injected calf muscle remained decreased 5 weeks following intramuscular BoNT-A injection. Furthermore, it has been reported that spastic type CP muscle volume grows at a much slower rate after BoNT-A injections (regardless of injection frequency) compared to typically developing controls. However neither of these recent studies involved a spastic type CP control group, receiving no BoNT-A, and therefore it was not possible to reconcile whether this slower growth rate is due to the BoNT-A injection or the underlying mechanisms that lead to reduced growth in spastic type CP in general. Muscle weakening from BoNT-A appears to be beneficial in the short-term for children with spastic type CP however until we know the precise time-course of changes which occur in muscle in response to BoNT-A in these children, it is difficult to predict the long term effect BoNT-A injections has on strength and subsequent function. This reasoning underpins the concerns expressed in the literature regarding the possible detrimental long-term effects of BoNT-A injections on muscle structure and function. It is proposed that this randomised controlled trial will assess the impact of BoNT-A injections treatment to the calf muscles. The research plan will provide a comprehensive picture of calf muscle growth in young children naive to BoNT-A and following their first treatment.
Interventions
This study observes the effect of BoNT-A treatment, currently standard best practice clinical care, for lower limb spasticity in children with CP. All participants with CP in this study will have a clinical indication for lower limb BoNT-A treatment and will receive all assessments, treatment and care that is prescribed by their treating paediatric specialist or orthopaedic surgeon. Participants will receive one intramuscular injection of BoNT-A treatment to the muscles of the lower leg as requi
This study observes the effect of BoNT-A treatment, currently standard best practice clinical care, for lower limb spasticity in children with CP. All participants with CP in this study will have a clinical indication for lower limb BoNT-A treatment and will receive all assessments, treatment and care that is prescribed by their treating paediatric specialist or orthopaedic surgeon. Participants will receive one intramuscular injection of BoNT-A treatment to the muscles of the lower leg as required a priori and performed by the participants treating paediatric specialist or orthopaedic surgeon. The source of the BoNT-A will be Botox (Registered Trademark, Allergan Pharmaceuticals). Total maximum dose of 7U/kg BoNT-A per leg will be administered with dilution 100units in 2ml saline. Medial and lateral gastrocnemius muscle: 4U/kg BoNT-A will be administered to four sites in the medial and lateral gastrocnemius (two sites medially and two sites laterally) as indicated by increased spasticity with active dorsiflexion, reduced passive ankle dorsiflexion range of motion while maintaining full knee extension and equinus gait during paediatric specialist and physiotherapy assessment. Soleus muscle: 2U/kg BoNT-A will be administered to one site in the soleus as indicated by reduced passive ankle dorsiflexion range of motion while maintaining knee flexed during paediatric specialist and physiotherapy assessment. Tibialis Posterior muscle: 1U/kg BoNT-A will be administered to one site in the tibialis posterior as indicated by a dynamic varus foot deformities during the stance phase of walking gait. To ensure the anatomically correct administration of the intramuscular BoNT-A injection, the site/s of the injection will be localised using ultrasound and/or electrical stimulation. Injections will be performed within 1 week following baseline measurements in the treatment group. The doses in the research project will be administered as above. However, participants who have been identified as clinically indicated for additional BoNT-A (e.g. upper limb BoNT-A) will receive this as part of standard clinical care and safe practice guidelines.
Sponsors
Dr Lee Barber
Study design
Allocation
Randomised controlled trial
Primary purpose
Treatment
Masking
Blinded (masking used) (Investigator)
Eligibility
Sex/Gender
All
Age
2 Years to 5 Years
Healthy volunteers
No
Inclusion criteria
1. Confirmed diagnosis of unilateral or bilateral spastic type CP with a predominant spastic motor type and more involvement of the lower limb. 2. Aged 2-5 years at study entry. 3. Gross Motor Functional Classification System (GMFCS) classification of I-II, independently ambulant. 4. Maximum passive ankle dorsiflexion greater than or equal to -5 degrees (5 degrees plantarflexed). 5. Prescribed intramuscular BoNT-A injection to the lower leg for spasticity treatment Sufficient co-operation and cognitive understanding to participate in the assessments.
Exclusion criteria
Exclusion Criteria: 1. Predominant lower limb dystonia motor type 2. Previous lower limb intramuscular BoNT-A injections 3. Previous lower limb surgical interventions 4. Contraindications for BoNT/A injection treatment
Outcome results
None listed