Effect of Dysport Injections on Energy Expenditure and Walking Efficiency in Children With Cerebral Palsy

Effect of Single Event Multi Level Chemoneurolysis With Dysport on Energy Expenditure and Walking Efficiency

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03469999

Enrollment

Registered

2018-03-19

Start date

2018-12-12

Completion date

2021-05-26

Last updated

2022-06-01

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Cerebral Palsy

Keywords

Botulinum toxin A, Walking efficiency, Spasticity, Dysport, Pediatric

Brief summary

This study aims to evaluate the efficacy of single event multi level chemoneurolysis with the abobotulinumtoxin A drug, Dysport®, on walking energy expenditure and gait in children with spastic diplegia cerebral palsy.

Detailed description

Cerebral Palsy (CP) is the leading cause of disability in children, with the most widespread type of CP being spastic CP which negatively affects physical function. Specifically it is reported that there is an increase in energy expenditure and oxygen consumption in children with CP. Single event multi level chemoneurolysis with abobotulinumtoxinA has been found to be an effective treatment for patients with spasticity to reduce energy expenditure by increasing walking efficiency; however many of these studies have conflicting methodological approaches. Therefore this study aims to evaluate the single event multilevel chemoneurolysis with Dysport® on energy expenditure and gait in children with spastic diplegia CP.

Interventions

DRUGDysport Injectable Product

Selected dose of medication will be determined by affected muscle(s), severity of spasticity, and the patient's body weight. We will follow the recommended total Dysport dose of 10-15 units/kg per limb, not to exceed 15 units/kg for unilateral lower limb, 30 units/kg for bilateral lower limb, or a total of 1000 units, whichever is lower in a given session.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

5 Years to 17 Years

Healthy volunteers

Inclusion criteria

* Age: 5-17 years. Must be \<18 prior to injection. * \>10 kilograms at screening and injection visits * Diagnosis of spastic diplegia or mild- to moderate spastic quadriplegia Cerebral Palsy * Gross Motor Function Classification System level: I, II, III * Ability to ambulate independently without aid, equinus gait * Absent of joint or bone deformities * Eligible to receive single-event multi-level chemoneurolysis (SEMLC) * Cooperative and tolerant to testing procedures during clinic screening * Presence of spasticity in one or both legs * Be on a stable dose and regimen if on any prescribed medication/s * Parent must have signed written informed consent and the Patient Authorization for Use and Release of Health and Research Study Information

Exclusion criteria

* Ankle contractures no more than -10 degrees with the knee extended * Hemiplegia * Wheelchair dependent * Received Botulinum toxin within previous 4 months * Uncontrolled epilepsy or certain types of seizures * Fracture in the study limb within previous 12 months * Infection or skin disorder at planned injection site * Shortness of breath or other respiratory issues * Uncontrolled clinically significant medical condition * Received phenol or alcohol block in the study limb within previous 6 months * Surgery in the study limb within previous 12 months * Serial casting within previous 12 months * New physiotherapy and/or orthotic regimen \<1 month before study start. (physiotherapy and/or orthotic regimen will be permitted if it began \>1 month before study start and maintained throughout study)

Design outcomes

Primary

Measure	Time frame	Description
Oxygen Consumption (ml/kg/Min)	Baseline (1 week prior to injection), 4 weeks post injection, 12 weeks post injection	Energy expenditure (oxygen consumption (VO2)) will be measured during the 6 minute walk test using a portable metabolic cart. The participants will use a 10 meter walkway to walk back and forth during the 6 minutes to coverage as much distance as possible. During this time they will be wearing a portable spirometric device that collects the oxygen consumption (VO2) per minute.

Secondary

Measure	Time frame	Description
Gait Velocity (cm/s)	Baseline (1 week prior to injection), 4 weeks post injection, 12 weeks post injection	Gait analysis will be measured by the GaitMat system while the child walks on the mat back and forth for five trials.
Muscle Spasticity Using MAS	Baseline (1 week prior to injection), 4 weeks post injection, 12 weeks post injection	The Modified Ashworth Scale (MAS) measures muscle spasticity during passive stretching. Scores are on a 6-point scale and include 0, 1, 1+, 2, 3, and 4. Scores range from 0 (better outcome), which indicates no increase in muscle tone/muscle spasticity to a score of 4 (worse outcome), which indicates a rigid muscle or maximum spasticity. Each subscale is independently scored and not combined to create a composite score. When calculating the mean score, 1+ is equivalent to a value of 1.5.
Muscle Spasticity Using MTS	Baseline (1 week prior to injection), 4 weeks post injection, 12 weeks post injection	The Modified Tardieu Scale (MTS) measures muscle spasticity during a passive stretch at both slow and fast speeds. Scores range from 0, which indicates no resistance throughout the course of the passive movement (better outcome), to 5, which indicates that the joint is immovable (worse outcome). The first measure determines the maximum range of motion of a target muscle group in degrees and the second measure determines the angle where muscle resistance is felt during a rapid velocity stretch, recorded in degrees. The total score is calculated by subtracting measure one from measure two. A greater difference between measures indicates less muscle spasticity. The Modified Tardieu Scale will be performed in the hamstrings, gastrocnemius, and soleus muscles.
Score on the Cerebral Palsy Quality of Life (CP QOL) Questionnaire	Baseline (1 week prior to injection), 4 weeks post injection, 12 weeks post injection	The Cerebral Palsy Quality of Life (CP QOL) Questionnaire consists of 66 items ranging from 1 to 9 with a lower score indicating a higher quality of life. The total score will be calculated as well as an individual score for the seven subscale domains: Social well-being and acceptance, functioning, Participation and physical health, Emotional well-being, Access to services, pain and feeling about disability, and family health. Scoring involves 2 steps. First, items are transformed to a scale with a possible range of 0-100. The scores are recoded as follows 1 to 0, 2 to 12.5, 3 to 25, 4 to 37.5, 5 to 50, 6 to 6.2, 7 to 75, 8 to 87.5, 9 to 100. Then the algebraic mean of item values is computed from the composite score for each domain. Once rescored, the final score ranges from 0 to 100, with 0 indicating a worse outcome.

Countries

United States

Participant flow

Participants by arm

Arm	Count
Dysport Injectable Product All participants will participate in baseline data collection of energy expenditure, gait analysis, and lower limb spasticity assessment. All participants will receive single event multi level chemoneurolysis with Dysport and will have repeat data collection at 4 weeks and 12 weeks post injection. Selected dose of medication will be determined by affected muscle(s), severity of spasticity, and the patient's body weight. We will follow the recommended total Dysport dose of 10-15 units/kg per limb, not to exceed 15 units/kg for unilateral lower limb, 30 units/kg for bilateral lower limb, or a total of 1000 units, whichever is lower in a given session.	12
Total	12

Arm

Count

Dysport Injectable Product

All participants will participate in baseline data collection of energy expenditure, gait analysis, and lower limb spasticity assessment. All participants will receive single event multi level chemoneurolysis with Dysport and will have repeat data collection at 4 weeks and 12 weeks post injection. Selected dose of medication will be determined by affected muscle(s), severity of spasticity, and the patient's body weight. We will follow the recommended total Dysport dose of 10-15 units/kg per limb, not to exceed 15 units/kg for unilateral lower limb, 30 units/kg for bilateral lower limb, or a total of 1000 units, whichever is lower in a given session.

Total

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Lost to Follow-up	2

Baseline characteristics

Characteristic	Dysport Injectable Product
Age, Continuous	11.5 years STANDARD_DEVIATION 3.4
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	0 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	12 Participants
Gross Motor Function Classification System (GMFCS) Diagnosis GMFCS I (Children walk at home, school, outdoors and in the community)	2 Participants
Gross Motor Function Classification System (GMFCS) Diagnosis GMFCS II (Children walk in most settings and climb stairs holding onto a railing)	7 Participants
Gross Motor Function Classification System (GMFCS) Diagnosis GMFCS III (Children walk using a hand-held mobility device in most indoor settings)	2 Participants
Gross Motor Function Classification System (GMFCS) Diagnosis Unknown (not part of analysis)	1 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	0 Participants
Race (NIH/OMB) Black or African American	0 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	12 Participants
Race (NIH/OMB) White	0 Participants
Region of Enrollment United States	12 participants
Sex: Female, Male Female	6 Participants
Sex: Female, Male Male	6 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 12
other Total, other adverse events	0 / 12
serious Total, serious adverse events	0 / 12

Outcome results

Primary

Oxygen Consumption (ml/kg/Min)

Energy expenditure (oxygen consumption (VO2)) will be measured during the 6 minute walk test using a portable metabolic cart. The participants will use a 10 meter walkway to walk back and forth during the 6 minutes to coverage as much distance as possible. During this time they will be wearing a portable spirometric device that collects the oxygen consumption (VO2) per minute.