Effect of botulinum toxin A injections and specific intensive rehabilitation therapy in children with hemiparetic cerebral palsy on upper limb functions and skills

ISRCTN	ISRCTN69541857
DOI	https://doi.org/10.1186/ISRCTN69541857
Protocol serial number	NL12005.096.06
Sponsor	Ipsen Biopharm Ltd (UK)
Funders	Rotterdam Foundation Child Rehabilitation Fund 'Adriaan Fund' (Stichting Rotterdams Kinderrevalidatie Fonds Adriaanstichting) (The Netherlands), Johanna Children's Fund (Johanna Kinderfonds) (The Netherlands) - http://www.johannakinderfonds.nl, Phelps Foundation for Spasticity (Phelps Stichting voor Spastici) (The Netherlands) - http://www.phelps-stichting.nl, Profile Fund of the University Hospital Maastricht (Profileringsfonds azM) (The Netherlands), Foundation for Children's Illness (Stichting het gebrekkige Kind) (The Netherlands), Ipsen Biopharm Ltd (UK) - provided Dysport®

Submission date: 04/12/2007
Registration date: 31/03/2008
Last edited: 20/08/2015

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Nervous System Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Mrs Lucianne Speth
Scientific

Franciscusoord Child Rehabilitation
Onderstestraat 29
Valkenburg
6301 KA
Netherlands

Phone	+31 (0)455 282 615
Email	LSpeth@T-Online.de

Study information

Primary study design	Interventional
Study design	Randomised controlled trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	Effect of botulinum toxin A injections and specific intensive rehabilitation therapy in children with hemiparetic cerebral palsy on upper limb functions and skills
Study acronym	BoBiVa (Botuline toxine Bimanuele Vaardigheden)
Study objectives	Research question: What is the effect of botulinum toxin A (btA) injections (B), an intensive physical and occupational therapy program aimed at improving arm function and skills (C), or a combination of both (A), on arm function, bimanual skills and use of the affected arm, in children with hemiparetic cerebral palsy, relative to the course in such children who receive usual care (D)?
Ethics approval(s)	1. Medical Ethics Committee of the Meuse Hospital (Medisch Ethische Toetsingscommissie Atrium MC-Maaslandziekenhuis), 27/07/2006 2. This trial is also registered at the Centrale Commissie Mensgebonden Onderzoek (CCMO) Central Committee for Research Involving Human Subjects (https://toetsingonline.ccmo.nl) (ref: NL12005.096.06)
Health condition(s) or problem(s) studied	Cerebral palsy
Intervention	This study will take place in three hospitals in the Netherlands: University Hospital Maastricht (Franciscusoord Valkenburg), Maartenskliniek Nijmegen Hospital and Free University Medical Centre (Vrije Universiteit Medisch Centrum [VUMC]) Amsterdam. Interventions: Group A: BtA injections (Dysport®) prior to therapy programme and intensive physical and occupational therapy programme Group B: BtA injections only Group C: Intensive physical and occupational therapy programme Group D: Usual care BtA injections: The most spastic muscles hampering function will be injected. Dysport® dilution: 25 U/0.1 ml, dose 6 - 9 U/kg body weight muscles above elbow, 3 - 6 U/kg body weight muscles in forearm, limited to no more than 150 units (0.6 ml) at any one injection site. In the intrinsic thumb muscles the maximum dose will be 25 U per muscle. A maximum Dysport® dose of 1,000 U per child in total per session will be used. Intensive physical and occupational therapy programme: Participants will receive one hour of ocupational therapy and 30 minutes of physical therapy, twice a week for 12 weeks.
Intervention type	Drug
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Botulinum toxin A (Dysport®)
Primary outcome measure(s)	1. Assisted Hand Assessment (AHA): original test kit for children 2.5 - 6 years and board game for children 7 - 12 years (T2, T4, T6) 2. A measure of manual ability for children with upper limb impairments (ABILHAND)-Kids questionnaire (T1 - T6) 3. Canadian Occupational Performance Measure (COPM): establishing treatment goals; Goal Attainment Scaling (GAS) of the most important bimanual treatment goal (T1, T4, T6) 4. Video recording of two fine motor tasks (children 7 - 12 years: buttering and cutting bread, screw construction task; children 2.5 - 6 years: building with 'poppons', threading beads) and one gross motor task (children 2.5 - 6 years: building blocks; children 7 - 12 years: stacking cylinders). These videos will be scored with newly developed and reliability tested Video Observation (VO) criteria (T2, T6). T1 and T2: Baseline T3: 6 weeks after btA and start of the therapy program T4: 12 weeks, end of therapy program T5: 18 weeks T6: 24 weeks
Key secondary outcome measure(s)	1. Wrist and elbow tone and Tardieu Scale or Spasticity Test (SPAT): supine and sitting (T1 - T6) 2. Active and passive range of motion (ROM) of wrist (with fisted hand and with extended fingers), and of elbow and thumb (T1 - T6) 3. Grip strength: E-link (biometrics®) and functional grip strength (T1 - T6) T1 and T2: Baseline T3: 6 weeks after btA and start of the therapy program T4: 12 weeks, end of therapy program T5: 18 weeks T6: 24 weeks
Completion date	01/01/2012

Eligibility

Participant type(s)	Patient
Age group	Child
Lower age limit	2.5 Years
Upper age limit	12 Years
Sex	All
Target sample size at registration	60
Key inclusion criteria	1. Aged 2.5 - 12 years, either sex 2. Cerebral palsy 3. Hagberg diagnosis: spastic hemiparesis or extreme asymmetric diplegia 4. Hand function impairment Zancolli grade I with evident problems in thumb extension and supination, Zancolli grade IIA and IIB 5. Mentally able to comprehend and perform tasks 6. Children and their parents should be able to cope with the intensive rehabilitation therapy programme and the measurement sessions 7. Children and the parents/caregivers should comprehend and speak Dutch 8. Children and their parents indicate the necessity for improvement of the children's abilities
Key exclusion criteria	1. Severe structural contractures of the muscles at the extremity to be treated: 1.1. Passive elbow extension maximum 160 degrees or less 1.2. Supination maximum 30 degrees or less from neutral position 1.3. Wrist dorsal flexion maximum 20 degrees or less in children aged 2.5 - 6 years, or 45 degrees or less in age group 7 - 12 years 2. Severe impairment of hand function: no active hand function is expected after treatment (Zancolli III) 3. Hand surgery or phenolisation or btA injections in the arm less than nine months ago 4. Contraindication for botulinum toxin (muscular diseases such as myasthenia gravis, tetanus vaccination less than three months before the injection, use of aminoglycoside antibiotics or spectinomycine and known hypersensitivity for human albumin) 5. Contraindication for anaesthesia 6. Children who cannot bear touching the affected arm and hand
Date of first enrolment	01/01/2008
Date of final enrolment	01/01/2012

Locations

Countries of recruitment

Netherlands

Study participating centre

Franciscusoord Child Rehabilitation

Valkenburg
6301 KA
Netherlands

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	19/08/2015		Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes
Study website	Study website	11/11/2025	11/11/2025	No	Yes