Clinical trial NCT02546999: Does Botulinum Toxin A Make Walking Easier in Children With Cerebral Palsy?
Official title: Does Botulinum Toxin A Make Walking Easier in Children With Cerebral Palsy?
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Cerebral Palsy
Muscle Spasticity
Keywords: Botulinum Toxins, Type A
Walking
Lead sponsor: St. Olavs Hospital
Sponsor class: OTHER
Collaborators: name: Norwegian University of Science and Technology
name: The Hospital of Vestfold
name: University Hospital of North Norway
name: Oslo University Hospital
name: Haukeland University Hospital
name: Fondation Lenval
name: Mazowieckie Centrum Neuropsychiatrii, Warszawa
First posted: 2015-09-11
Enrollment: 61
Sex: ALL
Minimum age (years): 4
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: In Norway, about 60% of all children with cerebral palsy (CP) are being treated with botulinum toxin A (BoNT-A) at 6 years of age, mainly in the legs. Despite this widespread use of the drug, the evidence for a positive effect on walking is insufficient. Moreover, large variation in effect is seen by clinicians. The main objective of the present study is to investigate whether injections with BoNT-A in the calf muscles make walking easier in children with spastic CP within 6 months, reflected by reduced energy cost during walking.

Detailed description: This is an industry independent multicentre clinical trial. The randomization will be done by a computer number random generator and will be carried out and held by the unit of Applied Clinical Research at NTNU. Two strata: age and center.

The study will be conducted according to Consort guidelines and guidelines for Good Clinical Practice. It is approved by the local Ethical committee (REK Nord) and the Norwegian Drug Agency.

Primary research question is: Do BoNT-A injections in the calf muscles make walking easier in children with CP? Secondary research questions: 1) Do BoNT-A injections in the calf muscles increase activity? 2) Do BoNT-A injections in the calf muscles improve walking capacity 3) Do BoNT-A injections in the calf muscles improve perceived performance and satisfaction related to mobility tasks and 4) Do BoNT-A injections in the calf muscles reduce recurrent musculoskeletal pain? The participants will receive the treatment with both local anaesthesia and conscious sedation with oral or nasal benzodiazepines.Outcome measures are made at baseline and 4, 12 and 24 weeks after treatment, with primary endpoint at 12 weeks.

Data will be analyzed using a linear mixed model (LMM). The difference in change in the primary outcome measure (energy cost during walking) between the treated and placebo groups will be done using a post hoc test following the LMM. Secondary, the same model will be used to test for an effect also at 4 and 24 weeks post injection. Age, GMFCS Level, number of prior BoNT-A treatments and study center will be considered as potential covariates.

A substudy will be conducted within the frames of this RCT, aiming to identify characteristics of those who respond to the treatment compared to those who do not respond (outcome measures 6, 7,8 and 9).

Eligibility criteria: Inclusion criteria:

* Diagnosed with unilateral or bilateral CP
* GMFCS level I and II
* Signed informed consent
* expected cooperation of the patients for the treatment and follow up.

Exclusion Criteria:

* BoNT-A injections in the lower legs in the last 6 months before intervention
* history of adverse reactions to BoNT-A
* Known hypersensitivity to BoNT-A or to any of the excipients
* Orthopedic surgery in the legs in the last 2 years
* Major cognitive impairments (must be able to take verbal instructions and conduct the test procedure)
* infection at the proposed injection site(s)
* Subclinical or clinical evidence of defective neuromuscular transmission e.g. myasthenia gravis or Lambert-Eaton Syndrome in patients with peripheral motor neuropathic diseases (e.g. amyotrophic lateral sclerosis or motor neuropathy)
* other underlying neurological disorders that may be affected by BoNT-A injections
* Use of aminoglycoside antibiotics or spectinomycin, or other medicinal products that interfere with neuromuscular transmission (e.g. neuromuscular blocking agents)
* Pregnant or breast-feeding
* Childbearing potential not using contraception
* any reason why, in the opinion of the investigator, the patient should not participate
* Children needing deep sedation under treatment

Primary outcomes:
measure: Energy cost during walking
timeFrame: 6 months
Secondary outcomes:
measure: Activity
timeFrame: 6 months
measure: Perceived improved performance and satisfaction
timeFrame: 6 months
measure: Recurrent musculoskeletal pain
timeFrame: 6 months
measure: Walking capacity
timeFrame: 6 months
Other outcomes:
measure: Gait pattern
timeFrame: 6 months
measure: Ankle strength
timeFrame: 6 months
measure: Spasticity
timeFrame: 6 months
measure: Self-perceived effect on walking
timeFrame: 4 weeks
Locations:
city: Nice
country: France
facility: Lenval Foundation Children's Hospital
city: Bergen
country: Norway
facility: Haukeland University Hospital
city: Oslo
country: Norway
facility: Oslo University Hospital
city: Tromsø
country: Norway
facility: University Hospital of North-Norway
city: Trondheim
country: Norway
facility: Department of Orthopaedic Surgery, St. Olavs University Hospital
city: Tønsberg
country: Norway
facility: Vestfold Hospital trust
city: Warsaw
country: Poland
facility: Mazowieckie Centrum Neuropsychiatrii, Zagorze
Study officials:
affiliation: St. Olavs Hospital
name: Petter Aadahl, md prof
role: STUDY_DIRECTOR
References:
citation: Braendvik SM, Roeleveld K, Andersen GL, Raftemo AE, Ramstad K, Majkic-Tajsic J, Lamvik T, Lund B, Follestad T, Vik T. The WE-Study: does botulinum toxin A make walking easier in children with cerebral palsy?: Study protocol for a randomized controlled trial. Trials. 2017 Feb 6;18(1):58. doi: 10.1186/s13063-016-1772-8.