Back to resultsBOTOX® Treatment in Pediatric Lower Limb Spasticity
Primary Purpose
Pediatrics, Muscle Spasticity, Cerebral Palsy
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
botulinum toxin Type A
Normal Saline (Placebo)
Sponsored by
About this trial
This is an interventional treatment trial for Pediatrics
Eligibility Criteria
Inclusion Criteria:
- Minimum weight of 10 kg/22 lb
- Cerebral palsy with dynamic muscle contracture /spasticity of the ankle
Exclusion Criteria:
- Muscular dystrophy, myasthenia gravis, Eaton-Lambert syndrome, amyotrophic lateral sclerosis, or mitochondrial disease
- Uncontrolled epilepsy
- Botulinum Toxin therapy of any serotype for any condition within the last 6 months
- History of surgical intervention of the lower study leg or planned surgery of any limb during the study
- Previous casting of the study limb for spasticity within 6 months or with a dynamic splint within 3 months, or planned casting or dynamic splinting for spasticity of the study limb or affected upper limb during the study
Sites / Locations
- AMS Neurology
- Harrison Clinical Management
- Children's Hospital Colorado Dept. of PM&R
- Associated Neurologists of Southern CT, P.C.
- New England Center for Clinical Research
- NW FL Clinical Research Group, LLC
- Axcess Medical Research, LLC
- Pediatric Neurology, PA
- Children's Healthcare of Atlanta Children's Rehabilitation Associates
- Rehab Institute of Chicago
- The Children's Mercy Hospital & Clinics
- Washington University School of Medicine
- Clinical Research Center of New Jersey
- NYU Hospital for Joint Diseases
- Columbia University Medical Center Dept. of Rehab. & Regenerative Medicine
- OnSite Clinical Solutions, LLC
- PMG Research of Charlotte, LLC
- Rhode Island Hospital
- Vanderbilt University Medical Center
- University of Texas Southwestern Medical Center
- Baylor College of Medicine Texas Children's Hospital
- Road Runner Research
- Seattle Children's Hospital
- Marshfield Clinic
- Semmelweis Egyetem- Ortopédiai Klinika
- Debrecen University Clinical Center, Orthopedic Clinic
- Istituto IRCCS G. Gaslini
- Daegu Fatima Hospital
- National Health Insurance Service Ilsan Hospital
- Seoul National University Hospital
- Asan Medical Center
- Samsung Medical Center
- Severance Hospital, Yonsei University Health System
- Philippine Orthopedic Center
- St. Luke's Medical Center-Quezon City
- Philippine Children's Medical Center
- Uniwersytecki Dzieciecy Szpita
- Uni Centrum Kliniczne
- Centrum Rehabilitacji Krok po Kroku
- Specjal. Gabinet Neurologiczny
- INTERMED, Lublin
- CRH ŻAGIEL MED, Lublin
- Szpital Wojewódzki Nr 2
- Neuro - Dzieci I Mlodziezy Aga
- NZOZ Mazowieckie Centrum
- Childrens Republic Hospital
- Smolensk Regional Hospital- Regional Budget State Healthcare institution
- Tyumen Regional Hospital #2 - State Budget Healthcare Institution of Tyumen region
- Maharaj Nakorn Chiang Mai Hospital, Chiang Mai University
- Srinagarind Hospital, Khon Kaen University
- Ankara Diskapi Yildrim Beyazit
- Kocaeli Üniversitesi
- Selçuk Üniversitesi
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
BOTOX® 4 U/kg
BOTOX® 8 U/kg
Normal Saline (Placebo)
Arm Description
Participants received intramuscular injections of BOTOX® (botulinum toxin Type A) 4 U per kg of body weight (4 U/kg) into specified muscles of the lower limb on Day 1. Participants received weekly physical therapy (PT).
Participants received intramuscular injections of BOTOX® (botulinum toxin Type A) 8 U per kg of body weight (8 U/kg) into specified muscles of the lower limb on Day 1. Participants received weekly PT.
Participants received intramuscular injections of normal saline (placebo) into specified muscles of the lower limb on Day 1. Participants received weekly PT.
Outcomes
Primary Outcome Measures
Average Change From Baseline in Modified Ashworth Scale-Bohannon (MAS-B) Ankle Score With Knee Extended at Weeks 4 and 6
The MAS-B was used to evaluate spasticity based on grading the resistance encountered in the principal muscle group (elbow and wrist) by means of passively moving a limb through its range of motion at a study specified velocity. The resistance encountered to passive stretch was graded using a 6-point scale where: 0=no increase in muscle tone (best) to 4=affected part(s) rigid in flexion or extension (worst). For analysis purposes, the MAS-B was recoded as follows: 0=1, 1=1, 1+=2, 2=3, 3=4, 4=5. The scores at Weeks 4 and 6 were averaged. A Mixed Model Repeated Measures (MMRM) model was used for analysis. A negative change from Baseline indicates improvement.
Average Clinical Global Impression (CGI) of Overall Change by Physician at Weeks 4 and 6
The CGI of overall change (improvement or worsening) was assessed by the physician considering the participant's clinical condition and severity of side effects using a 9-point scale where: -4=very marked worsening to +4=very marked improvement. The scores at Weeks 4 and 6 were averaged. A Mixed Model Repeated Measures (MMRM) model was used for analysis.
Secondary Outcome Measures
Goal Attainment Score (GAS) as Assessed by Physician Using a 6-Point Scale
Two functional goals, one active and one passive, were selected by the participant and family in consultation with the physician investigator and/or treating physical therapist relative to the lower limb impairment due to spasticity. The physician assessed the achievement of the goals using a 6-point scale: where -3=worse than start to +2=much more than expected: improvements clearly exceed the defined therapeutic goal. An Analysis of Covariance (ANCOVA) model was used for analysis.
Change From Baseline in Severity of Spasticity of the Ankle With Knee Extended and Knee Flexed (R2-R1) Calculated Using the Modified Tardieu Scale (MTS)
The MTS measured the difference between slow and fast range of motion (R2-R1) and respective change from baseline to each posttreatment office visit. The MTS of the ankle was used to determine the passive range of movement at different movement velocities, V1 (as slow as possible) and V3 (as fast as possible) with the relative difference between a slow and fast velocity passive stretch determining the dynamic component of the muscle contracture for the joint. The investigator measured 2 joint angles by goniometer: the R1 angle which is the angle of catch after a fast velocity (V3) stretch and the R2 angle defined as the passive joint range of movement following a slow velocity (V1) stretch. The R2-R1 value indicated the level of the dynamic component of spasticity in the joint. The difference between R2 and R1 range of motion and respective change from baseline to each posttreatment office visit on the MTS was derived. An Analysis of Covariance (ANCOVA) model was used for analysis.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01603628
Brief Title
BOTOX® Treatment in Pediatric Lower Limb Spasticity
Official Title
BOTOX® Treatment in Pediatric Lower Limb Spasticity: Double-blind Study
Study Type
Interventional
2. Study Status
Record Verification Date
July 2018
Overall Recruitment Status
Completed
Study Start Date
September 11, 2012 (Actual)
Primary Completion Date
June 28, 2017 (Actual)
Study Completion Date
June 28, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Allergan
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This study will evaluate the safety and efficacy of BOTOX® (botulinum toxin Type A) in pediatric patients with lower limb spasticity.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pediatrics, Muscle Spasticity, Cerebral Palsy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
384 (Actual)
8. Arms, Groups, and Interventions
Arm Title
BOTOX® 4 U/kg
Arm Type
Experimental
Arm Description
Participants received intramuscular injections of BOTOX® (botulinum toxin Type A) 4 U per kg of body weight (4 U/kg) into specified muscles of the lower limb on Day 1. Participants received weekly physical therapy (PT).
Arm Title
BOTOX® 8 U/kg
Arm Type
Experimental
Arm Description
Participants received intramuscular injections of BOTOX® (botulinum toxin Type A) 8 U per kg of body weight (8 U/kg) into specified muscles of the lower limb on Day 1. Participants received weekly PT.
Arm Title
Normal Saline (Placebo)
Arm Type
Placebo Comparator
Arm Description
Participants received intramuscular injections of normal saline (placebo) into specified muscles of the lower limb on Day 1. Participants received weekly PT.
Intervention Type
Biological
Intervention Name(s)
botulinum toxin Type A
Other Intervention Name(s)
BOTOX®
Intervention Description
Participants received intramuscular injections of botulinum toxin Type A into specified muscles of the lower limb on Day 1.
Intervention Type
Drug
Intervention Name(s)
Normal Saline (Placebo)
Intervention Description
Participants received intramuscular injections of normal saline (placebo) into specified muscles of the lower limb on Day 1.
Primary Outcome Measure Information:
Title
Average Change From Baseline in Modified Ashworth Scale-Bohannon (MAS-B) Ankle Score With Knee Extended at Weeks 4 and 6
Description
The MAS-B was used to evaluate spasticity based on grading the resistance encountered in the principal muscle group (elbow and wrist) by means of passively moving a limb through its range of motion at a study specified velocity. The resistance encountered to passive stretch was graded using a 6-point scale where: 0=no increase in muscle tone (best) to 4=affected part(s) rigid in flexion or extension (worst). For analysis purposes, the MAS-B was recoded as follows: 0=1, 1=1, 1+=2, 2=3, 3=4, 4=5. The scores at Weeks 4 and 6 were averaged. A Mixed Model Repeated Measures (MMRM) model was used for analysis. A negative change from Baseline indicates improvement.
Time Frame
Baseline (Day 1) to Weeks 4 and 6
Title
Average Clinical Global Impression (CGI) of Overall Change by Physician at Weeks 4 and 6
Description
The CGI of overall change (improvement or worsening) was assessed by the physician considering the participant's clinical condition and severity of side effects using a 9-point scale where: -4=very marked worsening to +4=very marked improvement. The scores at Weeks 4 and 6 were averaged. A Mixed Model Repeated Measures (MMRM) model was used for analysis.
Time Frame
Weeks 4 and 6
Secondary Outcome Measure Information:
Title
Goal Attainment Score (GAS) as Assessed by Physician Using a 6-Point Scale
Description
Two functional goals, one active and one passive, were selected by the participant and family in consultation with the physician investigator and/or treating physical therapist relative to the lower limb impairment due to spasticity. The physician assessed the achievement of the goals using a 6-point scale: where -3=worse than start to +2=much more than expected: improvements clearly exceed the defined therapeutic goal. An Analysis of Covariance (ANCOVA) model was used for analysis.
Time Frame
Weeks 8 and 12
Title
Change From Baseline in Severity of Spasticity of the Ankle With Knee Extended and Knee Flexed (R2-R1) Calculated Using the Modified Tardieu Scale (MTS)
Description
The MTS measured the difference between slow and fast range of motion (R2-R1) and respective change from baseline to each posttreatment office visit. The MTS of the ankle was used to determine the passive range of movement at different movement velocities, V1 (as slow as possible) and V3 (as fast as possible) with the relative difference between a slow and fast velocity passive stretch determining the dynamic component of the muscle contracture for the joint. The investigator measured 2 joint angles by goniometer: the R1 angle which is the angle of catch after a fast velocity (V3) stretch and the R2 angle defined as the passive joint range of movement following a slow velocity (V1) stretch. The R2-R1 value indicated the level of the dynamic component of spasticity in the joint. The difference between R2 and R1 range of motion and respective change from baseline to each posttreatment office visit on the MTS was derived. An Analysis of Covariance (ANCOVA) model was used for analysis.
Time Frame
Baseline (Day 1) to Weeks 2, 4, 6, 8 and 12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Minimum weight of 10 kg/22 lb
Cerebral palsy with dynamic muscle contracture /spasticity of the ankle
Exclusion Criteria:
Muscular dystrophy, myasthenia gravis, Eaton-Lambert syndrome, amyotrophic lateral sclerosis, or mitochondrial disease
Uncontrolled epilepsy
Botulinum Toxin therapy of any serotype for any condition within the last 6 months
History of surgical intervention of the lower study leg or planned surgery of any limb during the study
Previous casting of the study limb for spasticity within 6 months or with a dynamic splint within 3 months, or planned casting or dynamic splinting for spasticity of the study limb or affected upper limb during the study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rozalina Dimitrova
Organizational Affiliation
Allergan
Official's Role
Study Director
Facility Information:
Facility Name
AMS Neurology
City
Pasadena
State/Province
California
ZIP/Postal Code
91106
Country
United States
Facility Name
Harrison Clinical Management
City
Pomona
State/Province
California
ZIP/Postal Code
91767
Country
United States
Facility Name
Children's Hospital Colorado Dept. of PM&R
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Associated Neurologists of Southern CT, P.C.
City
Fairfield
State/Province
Connecticut
ZIP/Postal Code
06824
Country
United States
Facility Name
New England Center for Clinical Research
City
Stamford
State/Province
Connecticut
ZIP/Postal Code
06905
Country
United States
Facility Name
NW FL Clinical Research Group, LLC
City
Gulf Breeze
State/Province
Florida
ZIP/Postal Code
32561
Country
United States
Facility Name
Axcess Medical Research, LLC
City
Loxahatchee Groves
State/Province
Florida
ZIP/Postal Code
33470
Country
United States
Facility Name
Pediatric Neurology, PA
City
Orlando
State/Province
Florida
ZIP/Postal Code
32819
Country
United States
Facility Name
Children's Healthcare of Atlanta Children's Rehabilitation Associates
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30342
Country
United States
Facility Name
Rehab Institute of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
The Children's Mercy Hospital & Clinics
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64108
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Clinical Research Center of New Jersey
City
Voorhees
State/Province
New Jersey
ZIP/Postal Code
08043
Country
United States
Facility Name
NYU Hospital for Joint Diseases
City
New York
State/Province
New York
ZIP/Postal Code
10003
Country
United States
Facility Name
Columbia University Medical Center Dept. of Rehab. & Regenerative Medicine
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
OnSite Clinical Solutions, LLC
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28203
Country
United States
Facility Name
PMG Research of Charlotte, LLC
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28203
Country
United States
Facility Name
Rhode Island Hospital
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02903
Country
United States
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
University of Texas Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75235
Country
United States
Facility Name
Baylor College of Medicine Texas Children's Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Road Runner Research
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78258
Country
United States
Facility Name
Seattle Children's Hospital
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States
Facility Name
Marshfield Clinic
City
Marshfield
State/Province
Wisconsin
ZIP/Postal Code
54449
Country
United States
Facility Name
Semmelweis Egyetem- Ortopédiai Klinika
City
Budapest
ZIP/Postal Code
1113
Country
Hungary
Facility Name
Debrecen University Clinical Center, Orthopedic Clinic
City
Debrecen
ZIP/Postal Code
4032
Country
Hungary
Facility Name
Istituto IRCCS G. Gaslini
City
Genoa
ZIP/Postal Code
16148
Country
Italy
Facility Name
Daegu Fatima Hospital
City
Daegu
ZIP/Postal Code
41199
Country
Korea, Republic of
Facility Name
National Health Insurance Service Ilsan Hospital
City
Gyeonggi-do
ZIP/Postal Code
10444
Country
Korea, Republic of
Facility Name
Seoul National University Hospital
City
Seoul
ZIP/Postal Code
03080
Country
Korea, Republic of
Facility Name
Asan Medical Center
City
Seoul
ZIP/Postal Code
05505
Country
Korea, Republic of
Facility Name
Samsung Medical Center
City
Seoul
ZIP/Postal Code
06351
Country
Korea, Republic of
Facility Name
Severance Hospital, Yonsei University Health System
City
Seoul
ZIP/Postal Code
120-752
Country
Korea, Republic of
Facility Name
Philippine Orthopedic Center
City
Quezon City
ZIP/Postal Code
1100
Country
Philippines
Facility Name
St. Luke's Medical Center-Quezon City
City
Quezon City
ZIP/Postal Code
1102
Country
Philippines
Facility Name
Philippine Children's Medical Center
City
Quezon City
ZIP/Postal Code
1104
Country
Philippines
Facility Name
Uniwersytecki Dzieciecy Szpita
City
Białystok
ZIP/Postal Code
15-274
Country
Poland
Facility Name
Uni Centrum Kliniczne
City
Gdansk
ZIP/Postal Code
80-219
Country
Poland
Facility Name
Centrum Rehabilitacji Krok po Kroku
City
Gdansk
ZIP/Postal Code
80-389
Country
Poland
Facility Name
Specjal. Gabinet Neurologiczny
City
Krakow
ZIP/Postal Code
30-359
Country
Poland
Facility Name
INTERMED, Lublin
City
Lublin
ZIP/Postal Code
20-058
Country
Poland
Facility Name
CRH ŻAGIEL MED, Lublin
City
Lublin
ZIP/Postal Code
20-601
Country
Poland
Facility Name
Szpital Wojewódzki Nr 2
City
Rzeszów
ZIP/Postal Code
35-301
Country
Poland
Facility Name
Neuro - Dzieci I Mlodziezy Aga
City
Warsaw
ZIP/Postal Code
02-315
Country
Poland
Facility Name
NZOZ Mazowieckie Centrum
City
Warsaw
ZIP/Postal Code
05-462
Country
Poland
Facility Name
Childrens Republic Hospital
City
Kazan
ZIP/Postal Code
420138
Country
Russian Federation
Facility Name
Smolensk Regional Hospital- Regional Budget State Healthcare institution
City
Smolensk
ZIP/Postal Code
214018
Country
Russian Federation
Facility Name
Tyumen Regional Hospital #2 - State Budget Healthcare Institution of Tyumen region
City
Tyumen
ZIP/Postal Code
625039
Country
Russian Federation
Facility Name
Maharaj Nakorn Chiang Mai Hospital, Chiang Mai University
City
Chiang Mai
ZIP/Postal Code
50200
Country
Thailand
Facility Name
Srinagarind Hospital, Khon Kaen University
City
Khon Kaen
ZIP/Postal Code
40002
Country
Thailand
Facility Name
Ankara Diskapi Yildrim Beyazit
City
Ankara
ZIP/Postal Code
6110
Country
Turkey
Facility Name
Kocaeli Üniversitesi
City
Kocaeli
ZIP/Postal Code
41380
Country
Turkey
Facility Name
Selçuk Üniversitesi
City
Konya
ZIP/Postal Code
42250
Country
Turkey
12. IPD Sharing Statement
Links:
URL
http://www.allerganclinicaltrials.com
Description
Additional information on study locations near you may be found at AllerganClinicalTrials.com. For any study not on AllerganClinicalTrials.com, please contact IR-CTRegistration@Allergan.com for assistance.
Learn more about this trial
BOTOX® Treatment in Pediatric Lower Limb Spasticity
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