The WE-Study: does botulinum toxin A make walking easier in children with cerebral palsy?: Study protocol for a randomized controlled trial.
Intramuscular injections of botulinum toxin A (BoNT-A) have been a cornerstone in the treatment of spasticity for the last 20 years. In Norway, the treatment is now offered to two out of three children with spastic cerebral palsy (CP). However, despite its common use, the evidence for its functional effects is limited and inconclusive. The objective of this study is to determine whether BoNT-A makes walking easier in children with CP. We hypothesize that injections with BoNT-A in the calf muscles will reduce energy cost during walking, improve walking capacity, increase habitual physical activity, reduce pain and improve self-perceived performance and satisfaction.



This randomized, double-blinded, placebo-controlled, multicenter trial is conducted in a clinical setting involving three health regions in Norway. Ninety-six children with spastic CP, referred for single-level injections with BoNT-A in the calf muscles, will be invited to participate. Those who are enrolled will be randomized to receive either injections with BoNT-A (Botox®) or 0.9% saline in the calf muscles. Stratification according to age and study center will be made. The allocation ratio will be 1:1. Main inclusion criteria are (1) age 4 - 17.5 years, (2) Gross Motor Function Classification System levels I and II, (3) no BoNT-A injections in the lower limbs during the past 6 months and (4) no orthopedic surgery to the lower limbs during the past 2 years. The outcome measures will be made at baseline and 4, 12 (primary endpoint) and 24 weeks after injections. Primary outcome is change in energy cost during walking. Secondary outcomes are change in walking capacity, change in activity, perceived change in performance and satisfaction in mobility tasks, and pain. The primary analysis will use a linear mixed model to test for difference in change in the outcome measures between the groups. The study is approved by the Regional Ethical Committee and The Norwegian Medicines Agency. Recruitment started in September 2015.



The evaluation of effect is comprehensive and includes objective standardized tests and measures on both impairment and activity level. Results are to be expected by spring 2019.



ClinicalTrials.gov, NCT02546999 . Registered on 9 September 2015.
Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology, NTNU, Trondheim, Norway. siri.merete.brandvik@ntnu.no.|Clinical Services, St. Olav's University Hospital, Trondheim, Norway. siri.merete.brandvik@ntnu.no.
Siri Merete
SM
Brændvik
Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology, NTNU, Trondheim, Norway.
Karin
K
Roeleveld
Children's Center, Vestfold Hospital Trust, Tønsberg, Norway.|Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, NTNU, Trondheim, Norway.
Guro Lillemoen
GL
Andersen
Children's Center, Vestfold Hospital Trust, Tønsberg, Norway.
Anne Elisabeth Ross
AE
Raftemo
Department of Clinical Neurosciences for children, Oslo University Hospital, Oslo, Norway.
Kjersti
K
Ramstad
Division of Child and Adolescents Health, University Hospital of North Norway, Tromsø, Norway.
Jasmina
J
Majkic-Tajsic
Department of Orthopedics, St. Olav's University Hospital, Trondheim, Norway.
Torarin
T
Lamvik
Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, NTNU, Trondheim, Norway.|Department of Pediatrics, St. Olav's University Hospital, Trondheim, Norway.
Bendik
B
Lund
Department of Public Health and General Practice, Norwegian University of Science and Technology, NTNU, Trondheim, Norway.
Turid
T
Follestad
Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, NTNU, Trondheim, Norway.
Torstein
T
Vik
D065087:Acetylcholine Release Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D000293:Adolescent; D000367:Age Factors; D019274:Botulinum Toxins, Type A / Q000008:administration & dosage* / Q000009:adverse effects; D002547:Cerebral Palsy / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D002985:Clinical Protocols; D004185:Disability Evaluation; D004311:Double-Blind Method; D004734:Energy Metabolism; D017079:Exercise Tolerance; D005260:Female; D006801:Humans; D007273:Injections, Intramuscular; D016014:Linear Models; D008297:Male; D051346:Mobility Limitation; D009664:Norway; D010147:Pain Measurement; D017060:Patient Satisfaction; D020127:Recovery of Function; D012107:Research Design; D013997:Time Factors; D016896:Treatment Outcome; D016138:Walking
D065087:Acetylcholine Release Inhibitors; D019274:Botulinum Toxins, Type A; C545476:incobotulinumtoxinA
Activity; Botulinum toxin A; Cerebral palsy; Energy cost; Pain; Spasticity; Walking