Cerebral PalsyNCT02917967
A Pilot Study of the Effect of Botulinum Toxin Type a (Dysport®, Abobotulinum Toxin A) Injection on Changes in Musculotendinous Length and Dynamics of Hamstring Muscles During Gait in Children With Spastic Cerebral Palsy Walking With Excessive Knee Flexion
A study testing Botulinum toxin injection in people with Cerebral Palsy, run by Yonsei University at 1 site in South Korea.
Trial summary
This is a longitudinal, prospective, and open-label interventional study in a single center. We will investigate the effect of single injection in each patient. This study was designed to establish the clinical evidence for effect of botulinum toxin type a (Dysport, abobotulinum toxin A) injection on changes in… Read more about this study
- Who is it for?
- Ages 2 to 18 years
- Conditions the study is for
- Cerebral Palsy
- What is being tested?
- Botulinum toxin injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 1 siteSouth Korea
- Study dates
- 15 Nov 2016to 3 Sep 2018
- Phase
- Interventional
- 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 2 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Children with CP over the age of 2 years
- The spasticity is thought to interfere motor learning or cause abnormal posture and movement patterns by "management algorithm" of international consensus.
- MAS ≥ 1+ at hamstrings
- Dynamic spasticity rather than fixed contracture: Difference between Xv1 and Xv3 is at least 15 degrees in MTS at hamstrings
- I to III levels of GMFCS
Who cannot join
- Children who received interventions such as chemical nerve block or casting within 6 months
- Children who had baclofen pump
- Children who experienced the adverse reactions from previous BoNT-A injections
- Children who have a mixed type of CP (Athetosis, dystonia) or other movement disorder (eg. ataxia)
- Children who are participating in other investigational study at the moment
- Children who are not suitable for this study according to the investigator's discretion
Trial locations and contacts
1 site in 1 country.
South Korea1 site
Department of Rehabilitation Medicine, Severance Hospital, Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine
Seoul, 03722
About this study
This is a longitudinal, prospective, and open-label interventional study in a single center. We will investigate the effect of single injection in each patient. This study was designed to establish the clinical evidence for effect of botulinum toxin type a (Dysport, abobotulinum toxin A) injection on changes in musculotendinous length and dynamics of hamstring muscles during gait in children with spastic cerebral palsy walking with excessive knee flexion.
Baseline data such as Modified Ashworth scale (MAS), Modified Tardieu scale (MTS), Gross Motor Function Measures (GMFM), and Gross Motor Function Classification System (GMFCS) level will be assessed. Gait analysis will be performed using a computerized gait analysis system (VICON MX-T10 System with 6 infrared cameras, Oxford Metrics Inc., Oxford, UK) to measure the kinematic data (angle of each joint) during the gait cycle. A trained investigator will place 14 reflective markers on the anterior and posterior superior iliac spine, the mid points of the lateral femur, the lateral knee joint axis, the midpoints of the lateral tibia, the lateral malleolus, and the dorsal foot between metatarsal heads 2 and 3. All subjects should walk barefoot at a self-selected speed along an 8-meter path with the markers in place and the motion will be captured with a 100-Hz sampling frequency. Force-plates (AMTI OR 6-5, Advanced Mechanical Technology, Newton, MA, USA) under the path will record ground reaction forces during the walking trials with a 1000-Hz sampling frequency, and joint moments will be expressed as internal moments to counter the ground reaction forces. Data collection will continue until the subject achieved at least 3 'clean' force-plate strikes. Kinematic and kinetic data from successful trials will be used for statistical analysis. Video recording will be done simultaneously from the front, rear, and side, with the 3D gait analysis.
Read the detailed description
Based on the evaluation including gait analysis, we will select the target muscles and inject the toxin into the selected muscles of the spastic lower limb under the guidance of ultrasonography or electrical stimulation. After BoNT-A injection, these children will be evaluated after 1 month. Clinical data obtained in the baseline measurement will be assessed again. Motion capture data will also be collected. Finally, clinical data of patients will be collected 4 months after injection to identify the clinical improvement and side effects.
Motion capture data will be imported to OpenSim. We will generate an inverse kinematic analysis of each subject using following procedure:
- Scale the model to match the anthropometry of each subject. We will scale the dimensions of the torso, pelvis, thigh, shank, and foot based on the relative distances between pairs of markers measured experimentally and the corresponding markers in the model. The muscle attachments will also be scaled with the segment.
- Using a least-squares formulation, a set of desired joint angles for tracking, consistent with each scaled model, based on the marker trajectories, joint constraints, and joint angles from gait analysis will be computed.
- The musculotendinous length of each muscle will be calculated based on the "lower limb model 2010" by Arnold. This model adopted the wrapping surface to calculate the moment arm and musculotendinous unit passage at each joint. This model is intended to be used in research-graded kinematic analysis.
- Objectives <Primary objective>
1.To determine the changes of musculotendinous length of hamstrings after a single BoNT-A injection during walking in children with spastic CP walking with excessive knee flexion <Secondary objectives>
- To determine the efficacy on gross motor function after BoNT-A injection
- To determine the benefit on gait after BoNT-A injection
- To determine the efficacy on spasticity after BoNT-A injection
- To determine the kinematic change after BoNT-A injection
- To determine the dynamic change after BoNT-A injection
- To determine the treatment emergent adverse events following BoNT-A injection
- Subjects : total 32 children with cerebral palsy
- Intervention :
- BoNT-A will be injected into two hamstring and/or gastrocnemius muscles under the guidance of ultrasonography or electrical stimulation. 2. Maximal total dose and dose regimen for each muscle would follow the recommendation of international consensus. A. Semitendinosus 5 to 7.5 units/kg of body weight B. Semimembranosus 5 to 7.5 units/kg of body weight C. Gastrocnemius 10 units/kg of body weight D. Maximal total dose per patient : unilateral injection 500 units, bilateral injection 1,000 units E. The dosage of two hamstring muscles will depend on the severity of spasticity and gait abnormalities of children with CP
- Studies : 3D motion analysis, GMFM (gross motor function measure), GMFCS (gross motor function classification system), MAS (modified Ashworth scale), MTS (modified Tardieu scale)
- Evaluation plan : 1) pre-intervention, 2) post-4 weeks after intervention, 3) 16 weeks after intervention
- Conditions
- Cerebral Palsy
- Being tested
- Botulinum toxin injection
- Medical subject headings
- Cerebral Palsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Botulinum toxin injectionDrug
- BoNT-A will be injected into two hamstring and/or gastrocnemius muscles under the guidance of ultrasonography or electrical stimulation.
- Maximal total dose and dose regimen for each muscle would follow the recommendation of international consensus.
- Semitendinosus 5 to 7.5 units/kg of body weight B. Semimembranosus 5 to 7.5 units/kg of body weight C. Gastrocnemius 10 units/kg of body weight D. Maximal total dose per patient : unilateral injection 500 units, bilateral injection 1,000 units E. The dosage of two hamstring muscles will depend on the severity of spasticity and gait abnormalities of children with CP
| Study group | Role | What they receive |
|---|---|---|
| BTX injection group | Experimental | Botulinum toxin injection group Receives: Drug: Botulinum toxin injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in musculotendinous length of hamstrings
Changes in musculotendinous length of hamstrings obtained from 3D motion analysis after a single BoNT-A injection during walking in children with spastic CP walking with excessive knee flexion
Measured: pre-intervention (1 hour before intervention)
Changes in musculotendinous length of hamstrings
Changes in musculotendinous length of hamstrings obtained from 3D motion analysis after a single BoNT-A injection during walking in children with spastic CP walking with excessive knee flexion
Measured: 4 weeks after intervention
Changes in musculotendinous length of hamstrings
Changes in musculotendinous length of hamstrings obtained from 3D motion analysis after a single BoNT-A injection during walking in children with spastic CP walking with excessive knee flexion
Measured: 16 weeks after intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Sep 2016 (estimated)
- Study start15 Nov 2016
- Primary completion3 Sep 2018
- Study completion3 Sep 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cerebral PalsyStudies of the same condition, open and under way.
- More trials run by Yonsei UniversityThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yonsei University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02917967
- Sponsor's protocol ID
- 4-2016-0265
- Status last verified
- Jan 2019
- First submitted
- 27 Sep 2016
- Last updated
- 16 Jan 2019
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of the Effect of Botulinum Toxin Type a (Dysport®, Abobotulinum Toxin A) Injection on Changes in Musculotendinous Length and Dynamics of Hamstring Muscles During Gait in Children With Spastic Cerebral Palsy Walking With Excessive Knee Flexion
- ClinicalTrials.gov ID
- NCT02917967
- Acronym / sponsor ID
- 4-2016-0265
- Conditions
- Cerebral Palsy
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Yonsei UniversityUniversity, hospital or other
- Study start
- 15 Nov 2016
- Primary completion
- 3 Sep 2018 (actual)
- Study completion
- 3 Sep 2018 (actual)
- First posted
- 28 Sep 2016 (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.
This is a longitudinal, prospective, and open-label interventional study in a single center. We will investigate the effect of single injection in each patient. This study was designed to establish the clinical evidence for effect of botulinum toxin type a (Dysport, abobotulinum toxin A) injection on changes in musculotendinous length and dynamics of hamstring muscles during gait in children with spastic cerebral palsy walking with excessive knee flexion.
Baseline data such as Modified Ashworth scale (MAS), Modified Tardieu scale (MTS), Gross Motor Function Measures (GMFM), and Gross Motor Function Classification System (GMFCS) level will be assessed. Gait analysis will be performed using a computerized gait analysis system (VICON MX-T10 System with 6 infrared cameras, Oxford Metrics Inc., Oxford, UK) to measure the kinematic data (angle of each joint) during the gait cycle. A trained investigator will place 14 reflective markers on the anterior and posterior superior iliac spine, the mid points of the lateral femur, the lateral knee joint axis, the midpoints of the lateral tibia, the lateral malleolus, and the dorsal foot between metatarsal heads 2 and 3. All subjects should walk barefoot at a self-selected speed along an 8-meter path with the markers in place and the motion will be captured with a 100-Hz sampling frequency. Force-plates (AMTI OR 6-5, Advanced Mechanical Technology, Newton, MA, USA) under the path will record ground reaction forces during the walking trials with a 1000-Hz sampling frequency, and joint moments will be expressed as internal moments to counter the ground reaction forces. Data collection will continue until the subject achieved at least 3 'clean' force-plate strikes. Kinematic and kinetic data from successful trials will be used for statistical analysis. Video recording will be done simultaneously from the front, rear, and side, with the 3D gait analysis.
Detailed description
Based on the evaluation including gait analysis, we will select the target muscles and inject the toxin into the selected muscles of the spastic lower limb under the guidance of ultrasonography or electrical stimulation. After BoNT-A injection, these children will be evaluated after 1 month. Clinical data obtained in the baseline measurement will be assessed again. Motion capture data will also be collected. Finally, clinical data of patients will be collected 4 months after injection to identify the clinical improvement and side effects.
Motion capture data will be imported to OpenSim. We will generate an inverse kinematic analysis of each subject using following procedure:
- Scale the model to match the anthropometry of each subject. We will scale the dimensions of the torso, pelvis, thigh, shank, and foot based on the relative distances between pairs of markers measured experimentally and the corresponding markers in the model. The muscle attachments will also be scaled with the segment.
- Using a least-squares formulation, a set of desired joint angles for tracking, consistent with each scaled model, based on the marker trajectories, joint constraints, and joint angles from gait analysis will be computed.
- The musculotendinous length of each muscle will be calculated based on the "lower limb model 2010" by Arnold. This model adopted the wrapping surface to calculate the moment arm and musculotendinous unit passage at each joint. This model is intended to be used in research-graded kinematic analysis.
- Objectives <Primary objective>
1.To determine the changes of musculotendinous length of hamstrings after a single BoNT-A injection during walking in children with spastic CP walking with excessive knee flexion <Secondary objectives>
- To determine the efficacy on gross motor function after BoNT-A injection
- To determine the benefit on gait after BoNT-A injection
- To determine the efficacy on spasticity after BoNT-A injection
- To determine the kinematic change after BoNT-A injection
- To determine the dynamic change after BoNT-A injection
- To determine the treatment emergent adverse events following BoNT-A injection
- Subjects : total 32 children with cerebral palsy
- Intervention :
- BoNT-A will be injected into two hamstring and/or gastrocnemius muscles under the guidance of ultrasonography or electrical stimulation. 2. Maximal total dose and dose regimen for each muscle would follow the recommendation of international consensus. A. Semitendinosus 5 to 7.5 units/kg of body weight B. Semimembranosus 5 to 7.5 units/kg of body weight C. Gastrocnemius 10 units/kg of body weight D. Maximal total dose per patient : unilateral injection 500 units, bilateral injection 1,000 units E. The dosage of two hamstring muscles will depend on the severity of spasticity and gait abnormalities of children with CP
- Studies : 3D motion analysis, GMFM (gross motor function measure), GMFCS (gross motor function classification system), MAS (modified Ashworth scale), MTS (modified Tardieu scale)
- Evaluation plan : 1) pre-intervention, 2) post-4 weeks after intervention, 3) 16 weeks after intervention
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| BTX injection group | Experimental | Drug: Botulinum toxin injectionBotulinum toxin injection group |
Who may qualify
- Ages
- 2 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- Children with CP over the age of 2 years
- The spasticity is thought to interfere motor learning or cause abnormal posture and movement patterns by "management algorithm" of international consensus.
- I to III levels of GMFCS
Key exclusion criteria (6 listed)
- Children who received interventions such as chemical nerve block or casting within 6 months
- Children who had baclofen pump
- Children who experienced the adverse reactions from previous BoNT-A injections
- Children who have a mixed type of CP (Athetosis, dystonia) or other movement disorder (eg. ataxia)
- Children who are participating in other investigational study at the moment
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 |
|---|---|---|
| Botulinum toxin injection1. BoNT-A will be injected into two hamstring and/or gastrocnemius muscles under the guidance of ultrasonography or electrical stimulation. 2. Maximal total dose and dose regimen for each muscle would follow the recommendation of international consensus. A. Semitendinosus 5 to 7.5 units/kg of body weight B. Semimembranosus 5 to 7.5 units/kg of body weight C. Gastrocnemius 10 units/kg of body weight D. Maximal total dose per patient : unilateral injection 500 units, bilateral injection 1,000 units E. The dosage of two hamstring muscles will depend on the severity of spasticity and gait abnormalities of children with CP | Drug | BTX injection group |
Primary outcome
Changes in musculotendinous length of hamstrings
Time frame: pre-intervention (1 hour before intervention)
Changes in musculotendinous length of hamstrings obtained from 3D motion analysis after a single BoNT-A injection during walking in children with spastic CP walking with excessive knee flexion
Changes in musculotendinous length of hamstrings
Time frame: 4 weeks after intervention
Changes in musculotendinous length of hamstrings obtained from 3D motion analysis after a single BoNT-A injection during walking in children with spastic CP walking with excessive knee flexion
Changes in musculotendinous length of hamstrings
Time frame: 16 weeks after intervention
Changes in musculotendinous length of hamstrings obtained from 3D motion analysis after a single BoNT-A injection during walking in children with spastic CP walking with excessive knee flexion
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 16 Jan 2019.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Botulinum toxin injection in people with Cerebral Palsy, run by Yonsei University at 1 site in South Korea.
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 5 inclusion and 6 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 16 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
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?
Changes in musculotendinous length of hamstrings (time frame: pre-intervention (1 hour before intervention)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 16 Jan 2019.