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

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.

Study Overview

• Status: Completed
• Conditions: Cerebral Palsy
• Intervention / Treatment: Drug: Dysport Injectable Product

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.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Columbia University Irving Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 17 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

Drug: Dysport 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.; Other Names: Botulinum toxin A

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline (1 week prior to injection), 4 weeks post injection, 12 weeks post injection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gait Velocity (cm/s)	Gait analysis will be measured by the GaitMat system while the child walks on the mat back and forth for five trials.	Baseline (1 week prior to injection), 4 weeks post injection, 12 weeks post injection
Muscle Spasticity Using MAS	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.	Baseline (1 week prior to injection), 4 weeks post injection, 12 weeks post injection
Muscle Spasticity Using MTS	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.	Baseline (1 week prior to injection), 4 weeks post injection, 12 weeks post injection
Score on the Cerebral Palsy Quality of Life (CP QOL) Questionnaire	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.	Baseline (1 week prior to injection), 4 weeks post injection, 12 weeks post injection

Collaborators and Investigators

• Sponsor: Columbia University
• Investigators: Principal Investigator: Heakyung Kim, MD, Columbia University Medical Center- Department of Rehabilitation

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2018
• Primary Completion (Actual): May 26, 2021
• Study Completion (Actual): May 26, 2021

Study Registration Dates

• First Submitted: January 24, 2018
• First Submitted That Met QC Criteria: March 16, 2018
• First Posted (Actual): March 19, 2018

Study Record Updates

• Last Update Posted (Actual): June 1, 2022
• Last Update Submitted That Met QC Criteria: May 31, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Botulinum toxin A; Pediatric; Spasticity; Dysport; Walking efficiency
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Damage, Chronic; Cerebral Palsy; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Cholinergic Agents; Membrane Transport Modulators; Acetylcholine Release Inhibitors; Neuromuscular Agents; Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA
• Other Study ID Numbers: AAAR1322

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes