Does Botulinum Toxin A Make Walking Easier in Children With Cerebral Palsy?

Cerebral Palsy Clinical Trial

— WE  

Official title:

Does Botulinum Toxin A Make Walking Easier in Children With Cerebral Palsy?

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02546999
• Other study ID #: 2013/1195
• Secondary ID: 2014-002539-32
• Status: Completed
• Phase: Phase 4
• Start date: September 2015
• Est. completion date: October 15, 2021

Study information

• Verified date: January 2022
• Source: St. Olavs Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 61
• Est. completion date: October 15, 2021
• Est. primary completion date: October 15, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 4 Years to 17 Years

Eligibility

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

Related Conditions & MeSH terms

• Cerebral Palsy
• Muscle Spasticity

Intervention

Drug:
• botox
The agent will be given only once at point zero in the time scheme for the project.
• placebo
The agent will be given only once at point zero in the time scheme for the project.

Locations

Country	Name	City	State
France	Lenval Foundation Children's Hospital	Nice
Norway	Haukeland University Hospital	Bergen
Norway	Oslo University Hospital	Oslo
Norway	Vestfold Hospital trust	Tønsberg
Norway	University Hospital of North-Norway	Tromsø
Norway	Department of Orthopaedic Surgery, St. Olavs University Hospital	Trondheim
Poland	Mazowieckie Centrum Neuropsychiatrii, Zagorze	Warsaw

Sponsors (8)

Lead Sponsor	Collaborator
St. Olavs Hospital	Fondation Lenval, Haukeland University Hospital, Mazowieckie Centrum Neuropsychiatrii, Warszawa, Norwegian University of Science and Technology, Oslo University Hospital, The Hospital of Vestfold, University Hospital of North Norway

Countries where clinical trial is conducted

France,  Norway,  Poland, 

References & Publications (1)

Brændvik 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Gait pattern	3D gait analysis will be carried out on a subset of participants.	6 months
Other	Ankle strength	Isometric strength of ankle plantar- and dorsiflexors, will be made on a subset of the participants.	6 months
Other	Spasticity	Will be assessed by the use of Tardieu scale. On a subset of participants, concurrent velocity, position and muscle activation will be measured.	6 months
Other	Self-perceived effect on walking	A qualitative interview will be conducted on a subset of the participants at baseline and post 1 (4 weeks post injection)	4 weeks
Primary	Energy cost during walking	Will be measured by a 5 minutes walk test (overground walking at comfortable speed) with simultaneous gas exchange.	6 months
Secondary	Activity	Daily activity, measured by a body worn accelerometer over 4 periods of 7 consecutive days.	6 months
Secondary	Perceived improved performance and satisfaction	Assessed by The Canadian Occupational Performance Measure	6 months
Secondary	Recurrent musculoskeletal pain	Assessed by the Child Health Questionnaire (Norwegian version), and elements from the Brief Pain Inventory (Norwegian version)	6 months
Secondary	Walking capacity	Assessed with OMNI-RPE (OMNI Rating of Perceived Exertion) and a 1 Minute walk test at maximal gait speed	6 months