Cerebral PalsyPhase 4WENCT02546999
Does Botulinum Toxin A Make Walking Easier in Children With Cerebral Palsy?
A Phase 4 study testing botox in people with Cerebral Palsy and Muscle Spasticity, run by St. Olavs Hospital at 7 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 4 to 17 years
- Conditions the study is for
- Cerebral Palsy, Muscle Spasticity
- What is being tested?
- botox
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 61 participants
- Where
- 7 sitesin 3 countries
- Study dates
- Sep 2015to 15 Oct 2021
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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)
Show all 13Show fewer
- 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
Trial locations and contacts
7 sites in 3 countries.
7 sites in 3 countries
Norway5 sites
Haukeland University Hospital
Bergen, 5000
Oslo University Hospital
Oslo
Vestfold Hospital trust
Tønsberg
University Hospital of North-Norway
Tromsø
Department of Orthopaedic Surgery, St. Olavs University Hospital
Trondheim
About this study
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.
Read the 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).
- Conditions
- Cerebral Palsy, Muscle Spasticity
- Being tested
- botox, placebo
- Keywords
- Botulinum Toxins, Type A, Walking
- Medical subject headings
- Cerebral Palsy, Muscle Spasticity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
botoxDrug
Also called botulinum toxin A
The agent will be given only once at point zero in the time scheme for the project.
placeboDrug
Also called sodium chloride
The agent will be given only once at point zero in the time scheme for the project.
| Study group | Role | What they receive |
|---|---|---|
| botox | Experimental | Botox® (onabotulinumtoxin A),injections in the calf muscles. The total maximum body dose of Botox® in this study will be 420 Units. Maximum dose per injection site will be 50 Units. The gastrocnemius muscle will receive 5-6 Units Botox® per kg, but maximum 180 Units in each leg. The soleus muscle will receive 2 Units Botox® per kg with maximum dose 60 Units in each leg. Dilution: 100 Units Botox® in 1 ml 0.9% sodium chloride, and the maximum volume per injection site will be 0,5 ml in both study groups. The route of administration is intramuscular injection. Receives: Drug: botox |
| placebo | Placebo comparator | Sterile 0,9% Sodium Chloride injection The placebo dose will be the same dose in ml as the reconstituted Botox Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Energy cost during walking
Will be measured by a 5 minutes walk test (overground walking at comfortable speed) with simultaneous gas exchange.
Measured: 6 months
Secondary outcomes (4)
Activity
Daily activity, measured by a body worn accelerometer over 4 periods of 7 consecutive days.
Measured: 6 months
Perceived improved performance and satisfaction
Assessed by The Canadian Occupational Performance Measure
Measured: 6 months
Recurrent musculoskeletal pain
Assessed by the Child Health Questionnaire (Norwegian version), and elements from the Brief Pain Inventory (Norwegian version)
Measured: 6 months
Walking capacity
Assessed with OMNI-RPE (OMNI Rating of Perceived Exertion) and a 1 Minute walk test at maximal gait speed
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Sep 2015 (estimated)
- Study startSep 2015
- Primary completion15 Oct 2021
- Study completion15 Oct 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Cerebral PalsyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 61 participants (actual)
Sponsor and investigators
- Lead sponsor
- St. Olavs Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Norwegian University of Science and Technology, The Hospital of Vestfold, University Hospital of North Norway, Oslo University Hospital, Haukeland University Hospital, Fondation Lenval, Mazowieckie Centrum Neuropsychiatrii, Warszawa
- Responsible party
- Sponsor
- Investigators
- Petter Aadahl, md prof, Study director, St. Olavs Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02546999
- Sponsor's protocol ID
- 2013/1195
- Other IDs
- 2014-002539-32, 2014
- Acronym
- WE
- Status last verified
- Jan 2022
- First submitted
- 9 Sep 2015
- Last updated
- 11 Jan 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 28166806Braendvik SM, Ross Raftemo AE, Roeleveld K, Andersen GL, Ramstad K, Follestad T, Aarli A, Bonikowski M, Vik T; Walking Easier. Does botulinum neurotoxin A make walking easier in children with cerebral palsy? A randomized clinical trial. Dev Med Child Neurol. 2025 Feb;67(2):263-271. doi: 10.1111/dmcn.16038. Epub 2024 Jul 26.
PubMed 39058740
Study at a glance
From the registry record, last updated by the sponsor on 11 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Does Botulinum Toxin A Make Walking Easier in Children With Cerebral Palsy?
- ClinicalTrials.gov ID
- NCT02546999
- Acronym / sponsor ID
- WE / 2013/1195
- Conditions
- Cerebral Palsy, Muscle Spasticity
- Keywords
- Botulinum Toxins, Type A, Walking
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 61 participants (actual)
- Lead sponsor
- St. Olavs HospitalUniversity, hospital or other
- Collaborators
- Norwegian University of Science and Technology, The Hospital of Vestfold, University Hospital of North Norway, Oslo University Hospital, Haukeland University Hospital, Fondation Lenval, Mazowieckie Centrum Neuropsychiatrii, Warszawa
- Study start
- Sep 2015
- Primary completion
- 15 Oct 2021 (actual)
- Study completion
- 15 Oct 2021 (actual)
- First posted
- 11 Sep 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| botox | Experimental | Drug: botoxBotox® (onabotulinumtoxin A),injections in the calf muscles. The total maximum body dose of Botox® in this study will be 420 Units. Maximum dose per injection site will be 50 Units. The gastrocnemius muscle will receive 5-6 Units Botox® per kg, but maximum 180 Units in each leg. The soleus muscle will receive 2 Units Botox® per kg with maximum dose 60 Units in each leg. Dilution: 100 Units Botox® in 1 ml 0.9% sodium chloride, and the maximum volume per injection site will be 0,5 ml in both study groups. The route of administration is intramuscular injection. |
| placebo | Placebo comparator | Drug: placeboSterile 0,9% Sodium Chloride injection The placebo dose will be the same dose in ml as the reconstituted Botox |
Who may qualify
- Ages
- 4 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (13 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| botoxAlso: botulinum toxin AThe agent will be given only once at point zero in the time scheme for the project. | Drug | botox |
| placeboAlso: sodium chlorideThe agent will be given only once at point zero in the time scheme for the project. | Drug | placebo |
Primary outcome
Energy cost during walking
Time frame: 6 months
Will be measured by a 5 minutes walk test (overground walking at comfortable speed) with simultaneous gas exchange.
4 secondary outcomes
Activity
Time frame: 6 months
Perceived improved performance and satisfaction
Time frame: 6 months
Recurrent musculoskeletal pain
Time frame: 6 months
Walking capacity
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jan 2022.
- Background: PubMed 28166806Braendvik 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.
- Derived from this study: PubMed 39058740Braendvik SM, Ross Raftemo AE, Roeleveld K, Andersen GL, Ramstad K, Follestad T, Aarli A, Bonikowski M, Vik T; Walking Easier. Does botulinum neurotoxin A make walking easier in children with cerebral palsy? A randomized clinical trial. Dev Med Child Neurol. 2025 Feb;67(2):263-271. doi: 10.1111/dmcn.16038. Epub 2024 Jul 26.
Related trials for Cerebral Palsy
Not yet recruitingObservational study
Changes in Land-Based Motor Function After Routine Hydrotherapy in Children With Cerebral Palsy
Cerebral Palsy
Recruiting
MindEx: A Novel, Multifocal, Cognitive Brain-Machine Interface System
Paralysis; Quadriplegic, Quadraplegia
Not yet recruiting
EFFECT OF ROBOTIC GLOVES TRAINING ON UPPER LIMB COORDINATION, SELECTIVE MOTOR CONTROL AND ACTIVITIES OF DAILY LIVING IN CHILDREN WITH HEMIPARETIC CEREBRAL PALSY.
Hemiplegic Cerebral Palsy
RecruitingObservational study
Investigating Complex Neurodegenerative Disorders Related to Amyotrophic Lateral Sclerosis and Frontotemporal Dementia
Frontotemporal Dementia, Amyotrophic Lateral Sclerosis
Recruiting
Combined Popliteal and Adductor Canal Blocks for Postoperative Analgesia in Children With Cerebral Palsy
Cerebral Palsy, Postoperative Pain
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Petter Aadahl, md prof study director
St. Olavs Hospital
7 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing botox in people with Cerebral Palsy and Muscle Spasticity, run by St. Olavs Hospital at 7 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Norway, France, Poland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Energy cost during walking (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02546999, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jan 2022.