Short Term Follow-up of a Botulinum Toxin Intervention in... | NCT05126693

Status Module

Name	Class
KU Leuven	OTHER

Description Module

Detailed Description

Aim:

This study investigates the effect of integrated Botulinum Neurotoxin A (BoNT) treatment on morphologic muscle and tendon properties (muscle length and muscle volume, assessed with a 3D ultrasound measurement), spasticity and joint stiffness (measured with an instrumented spasticity assessment), joint range of motion (measured through goniometry), muscle strength (measured using dynamometry), gait (assessed through 3D gait analysis) and gross motor function (assessed using clinical test batteries). The aim is twofold: (1) determine whether integrated BoNT treatment of the medial gastrocnemius and the semitendinosus muscle(s) leads to changes in the morphologic muscle and tendon properties of the medial gastrocnemius and the semitendinosus muscle(s), the ankle and knee range of motion, spasticity, stiffness, muscle strength and gait, and (2) determine the correlation between baseline morphologic muscle and tendon properties and the changes in the primary outcome parameters (spasticity and stiffness) following the BoNT-treatment.

Design:

The current study has a non-randomized controlled design. Because BoNT is proven an effective treatment to reduce spasticity and improve gross motor function, it cannot be clinically justified to allocate children to a non-treatment group, if a new BoNT treatment is required. Delayed BoNT treatment could rapidly increase musculoskeletal impairments. It is therefore considered unethical to temporarily withdraw BoNT treatment from patients. To compensate the lack of randomization accurate matching of groups is required. Children will be matched on diagnosis (uni/bilateral CP), GMFCS level, age and spasticity level.

BoNT-treatment:

All children in the intervention group will receive BoNT injections in the medial gastrocnemius and/or the semitendinosus muscle(s) (other muscles may also be treated as part of multilevel treatment). As part of the standard integrated treatment approach of the CP Reference Centre of the University Hospitals Leuven, the injections are followed by a period of bilateral stretching casts if indicated (below the knee walking casts and removable knee extension casts when necessary) and all children will receive intensive physical therapy and application of orthotic management following BoNT injections. The follow-up period for the current study is 8-10 weeks. During this intensive physical therapy post-BoNT, the children in the intervention group will work on individualized treatment goals. These goals will be defined based on the baseline measurements during a multidisciplinary discussion with the treating physician, which is scheduled prior to the BoNT treatment. The fulfillment of these patient-specific goals will be evaluated by the Goal Attainment Score (GAS). During the follow-up period, the treating physical therapist will be interviewed on a two-weekly basis to verify whether and to what extend the therapy is focused on the personal treatment goals. Assessments of morphologic muscle and tendon properties, spasticity, stiffness, joint range of motion, muscle strength, and gait of the participants will be performed before the BoNT injections, and 8-10 weeks after the injection. This period of 8-10 weeks follow-up post BoNT injections was found to be appropriate, since the potential effect of BoNT on gross motor function is expected to be optimal after 6-10 weeks.

Study groups:

The study will include patients who are diagnosed with spastic CP, aged between 4 and 11 years and with Gross Motor Function Classification System (GMFCS) level I-III. The intervention and control group will be group-matched based on diagnosis (uni/lateral CP), GMFCS level, age and spasticity level.

Overall exclusion criteria were: BoNT injections less than 6 months before inclusion, a treatment history that includes previous selective dorsal rhizotomy treatment or a bony surgery less than 2 years before inclusion, and limited cooperation that would prevent a proper assessment. For all enrolled children, intensive rehabilitation post BoNT injections had to be foreseen as the standard care. For the intervention group, 30 children with a clinical indication for BoNT injections in the medial gastrocnemius and/or semitendinosus muscle(s) will be recruited, while for the control group, 30 children without an indication for a specific intervention in the next 3 months will be recruited.

For the intervention group, the baseline measures will be followed by the BoNT injections combined with casting and goal-oriented physical therapy (as described above), and the follow-up assessments will be planned 8-10 weeks post BoNT injections. Baseline and follow-up assessments for the intervention groups include 3D ultrasound, the instrumented spasticity measurement, functional strength tests, and 3D gait analysis.

The children in the control group will also be assessed twice with an interval of 8-10 weeks. During the 8-10 weeks, they will continue their usual care or normal routine treatment, i.e. regular physiotherapy and orthotic devices. Baseline and follow-up assessments for the control group include 3D ultrasound, the instrumented spasticity measurement and functional strength tests.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Intervention group	Experimental	The children in the intervention group will receive BoNT injections in the medial gastrocnemius and/or the semitendinosus muscle(s). As part of the standard treatment approach of the CP Reference Centre of the University Hospitals Leuven, the injections are followed by a period of bilateral stretching casts if indicated (below the knee walking casts and removable knee extension casts when necessary) and all children will receive intensive physical therapy and application of ankle foot orthoses following BoNT injections. The follow-up period for the current study is 8-10 weeks. During this intensive physical therapy period post-BoNT, the children in the intervention group will work on individualized treatment goals, which will be defined based on the baseline measurements during a multidisciplinary discussion with the treating physician (that is scheduled prior to the BoNT injections).	Other: Botulinum Toxin treatment combined with a post-BoNT intensive physical therapy period guided by individualized treatment goals.
Control group	No Intervention	This group will continue their usual care or normal routine treatment, i.e. physiotherapy and orthotic management during a period of 8-10 weeks.

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Botulinum Toxin treatment combined with a post-BoNT intensive physical therapy period guided by individualized treatment goals.	Other	BoNT treatment combined with a follow-up period of intensive physical therapy of 8-10 weeks. During this intensive physical therapy post BoNT injections, the children in the intervention group will work on individualized treatment goals, which will be defined based on the baseline measurements during a multidisciplinary discussion with the treating physician (planned prior to the BoNT injections).

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change in Normalized Muscle Volume of the Medial Gastrocnemius and the Distal Compartment of the Semitendinosus	Estimation of the muscle belly volume by three-dimensional freehand ultrasonography normalized to the product of body weight and height	Between baseline and 8-10 weeks after the BoNT injections for the intervention group, and between baseline and 8-10 weeks later for the control group.
Change in Echogenicity Intensity of the Medial Gastrocnemius and the Distal Compartment of the Semitendinosus	Estimation of the echogenicity intensity of the whole muscle volume by three-dimensional freehand ultrasonography. Echogenicity is expressed in arbitrary units ranging from 0 to 255. Higher values indicate lighter images, which indirectly suggests the presence of more non-contractile muscle tissue.	Between baseline and 8-10 weeks after the BoNT injections for the intervention group, and between baseline and 8-10 weeks later for the control group.
Absolute Muscle Volume Growth Rate of the Medial Gastrocnemius and the Distal Compartment of the Semitendinosus	Estimation of the absolute muscle volume growth rate, calculated by: (muscle volume (mL)post-muscle volume pre)/(age (months)post-age (months)pre)	Between baseline and 8-10 weeks after the BoNT injections for the intervention group, and between baseline and 8-10 weeks later for the control group.
Change in Kinematic Parameters	Estimation of the kinematic parameters throughout the whole gait cycle by three-dimensional gait analysis.	Between baseline and 8-10 weeks after the BoNT injections
Change in Gait Profile Score (Degrees)	The Gait Profile Score (GPS) is a summary measure derived from three-dimensional gait analysis that quantifies the overall deviation of a patient's gait kinematics from a normative (typically developing) reference dataset. It is calculated as the root mean square difference between the patient's joint angle trajectories of the lower limb and the corresponding mean trajectories of typically developing individuals across a gait cycle. The GPS is expressed in degrees and is based on nine key kinematic variables: pelvic tilt, obliquity, rotation; hip flexion, abduction, rotation; knee flexion; ankle dorsiflexion; and foot progression angle, typically for both left and right sides. It provides a global index of gait abnormality, where lower scores indicate gait patterns closer to normal, and higher scores reflect greater kinematic deviation.

Secondary Outcomes

Measure	Description	Time Frame
Change in Normalized Muscle Tendon Unit Length of the Medial Gastrocnemius	Estimation of the muscle tendon unit length by three-dimensional freehand ultrasonography, expressed as a percentage of total leg length.	Between baseline and 8-10 weeks after the BoNT injections for the intervention group, and between baseline and 8-10 weeks later for the control group.

Eligibility Module

Name	Affiliation	Role
Kaat Desloovere, Prof. Dr.	UZ Leuven	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
UZ Leuven		Leuven	Vlaams-Brabant	3000	Belgium

PubMed Identifier	Type	Citation	Retractions
23791154	Background	Bar-On L, Aertbelien E, Molenaers G, Van Campenhout A, Vandendoorent B, Nieuwenhuys A, Jaspers E, Hunaerts C, Desloovere K. Instrumented assessment of the effect of Botulinum Toxin-A in the medial hamstrings in children with cerebral palsy. Gait Posture. 2014 Jan;39(1):17-22. doi: 10.1016/j.gaitpost.2013.05.018. Epub 2013 Jun 20.
23994052

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Intervention Group	The children in the intervention group will receive BoNT injections in the medial gastrocnemius and/or the semitendinosus muscle(s). As part of the standard treatment approach of the CP Reference Centre of the University Hospitals Leuven, the injections are followed by a period of bilateral stretching casts if indicated (below the knee walking casts and removable knee extension casts when necessary). All children will then undergo an intensive physical therapy program lasting 8-10 weeks. This post-BoNT therapy phase is guided by individualized treatment goals, which are established based on baseline assessments. These goals are determined during a multidisciplinary meeting with the treating physician, held prior to the BoNT injections. Thus, the intervention consists of BoNT treatment combined with an 8-10 week period of intensive physical therapy tailored to each child's specific therapeutic needs.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	May 10, 2022

Arm/Group Information

ID	Title	Description
BG000	Intervention Group	The children in the intervention group will receive BoNT injections in the medial gastrocnemius and/or the semitendinosus muscle(s). As part of the standard treatment approach of the CP Reference Centre of the University Hospitals Leuven, the injections are followed by a period of bilateral stretching casts if indicated (below the knee walking casts and removable knee extension casts when necessary). All children will then undergo an intensive physical therapy program lasting 8-10 weeks. This post-BoNT therapy phase is guided by individualized treatment goals, which are established based on baseline assessments. These goals are determined during a multidisciplinary meeting with the treating physician, held prior to the BoNT injections. Thus, the intervention consists of BoNT treatment combined with an 8-10 week period of intensive physical therapy tailored to each child's specific therapeutic needs.
BG001	Control Group	This group will continue their usual care or normal routine treatment, i.e. physiotherapy and orthotic management during a period of 8-10 weeks.
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG00025 BG00120 BG00245

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Categorical

Count of Participants

Participants

Title

Denominators

Categories

Medial Gastrocnemius

- ParticipantsOG00025
- ParticipantsOG00120

Title	Measurements
	OG000-0.08(-0.16 to 0.04)

Primary

Change in Echogenicity Intensity of the Medial Gastrocnemius and the Distal Compartment of the Semitendinosus

Estimation of the echogenicity intensity of the whole muscle volume by three-dimensional freehand ultrasonography. Echogenicity is expressed in arbitrary units ranging from 0 to 255. Higher values indicate lighter images, which indirectly suggests the presence of more non-contractile muscle tissue.

Semitendinosus:

Intervention group: n = 24 < 25 due to bad quality data Control group: n = 19 < 20 due to bad quality data

Posted

Median

Inter-Quartile Range

Arbitrary units ranging from 0 to 255

Between baseline and 8-10 weeks after the BoNT injections for the intervention group, and between baseline and 8-10 weeks later for the control group.

ID	Title	Description
OG000	Intervention Group	The children in the intervention group will receive BoNT injections in the medial gastrocnemius and/or the semitendinosus muscle(s). As part of the standard treatment approach of the CP Reference Centre of the University Hospitals Leuven, the injections are followed by a period of bilateral stretching casts if indicated (below the knee walking casts and removable knee extension casts when necessary). All children will then undergo an intensive physical therapy program lasting 8-10 weeks. This post-BoNT therapy phase is guided by individualized treatment goals, which are established based on baseline assessments. These goals are determined during a multidisciplinary meeting with the treating physician, held prior to the BoNT injections. Thus, the intervention consists of BoNT treatment combined with an 8-10 week period of intensive physical therapy tailored to each child's specific therapeutic needs.

Primary

Absolute Muscle Volume Growth Rate of the Medial Gastrocnemius and the Distal Compartment of the Semitendinosus

Estimation of the absolute muscle volume growth rate, calculated by: (muscle volume (mL)post-muscle volume pre)/(age (months)post-age (months)pre)

Semitendinosus:

Intervention group: n = 24 < 25 due to bad quality data Control group: n = 19 < 20 due to bad quality data

Posted

Median

Inter-Quartile Range

ml/month

Between baseline and 8-10 weeks after the BoNT injections for the intervention group, and between baseline and 8-10 weeks later for the control group.

ID	Title	Description
OG000	Intervention Group	The children in the intervention group will receive BoNT injections in the medial gastrocnemius and/or the semitendinosus muscle(s). As part of the standard treatment approach of the CP Reference Centre of the University Hospitals Leuven, the injections are followed by a period of bilateral stretching casts if indicated (below the knee walking casts and removable knee extension casts when necessary). All children will then undergo an intensive physical therapy program lasting 8-10 weeks. This post-BoNT therapy phase is guided by individualized treatment goals, which are established based on baseline assessments. These goals are determined during a multidisciplinary meeting with the treating physician, held prior to the BoNT injections. Thus, the intervention consists of BoNT treatment combined with an 8-10 week period of intensive physical therapy tailored to each child's specific therapeutic needs.
OG001	Control Group

Primary

Change in Kinematic Parameters

Estimation of the kinematic parameters throughout the whole gait cycle by three-dimensional gait analysis.

Control group: 3DGA was not performed

Posted

Median

Inter-Quartile Range

Degrees

Between baseline and 8-10 weeks after the BoNT injections

ID	Title	Description
OG000	Intervention Group	The children in the intervention group will receive BoNT injections in the medial gastrocnemius and/or the semitendinosus muscle(s). As part of the standard treatment approach of the CP Reference Centre of the University Hospitals Leuven, the injections are followed by a period of bilateral stretching casts if indicated (below the knee walking casts and removable knee extension casts when necessary). All children will then undergo an intensive physical therapy program lasting 8-10 weeks. This post-BoNT therapy phase is guided by individualized treatment goals, which are established based on baseline assessments. These goals are determined during a multidisciplinary meeting with the treating physician, held prior to the BoNT injections. Thus, the intervention consists of BoNT treatment combined with an 8-10 week period of intensive physical therapy tailored to each child's specific therapeutic needs.
OG001	Control Group	This group will continue their usual care or normal routine treatment, i.e. physiotherapy and orthotic management during a period of 8-10 weeks.

Primary

Change in Gait Profile Score (Degrees)

The Gait Profile Score (GPS) is a summary measure derived from three-dimensional gait analysis that quantifies the overall deviation of a patient's gait kinematics from a normative (typically developing) reference dataset. It is calculated as the root mean square difference between the patient's joint angle trajectories of the lower limb and the corresponding mean trajectories of typically developing individuals across a gait cycle. The GPS is expressed in degrees and is based on nine key kinematic variables: pelvic tilt, obliquity, rotation; hip flexion, abduction, rotation; knee flexion; ankle dorsiflexion; and foot progression angle, typically for both left and right sides. It provides a global index of gait abnormality, where lower scores indicate gait patterns closer to normal, and higher scores reflect greater kinematic deviation.

Control group: 3DGA was not performed

Posted

Median

Inter-Quartile Range

Degrees

Between baseline and 8-10 weeks after the BoNT injections

ID	Title	Description
OG000	Intervention Group	The children in the intervention group will receive BoNT injections in the medial gastrocnemius and/or the semitendinosus muscle(s). As part of the standard treatment approach of the CP Reference Centre of the University Hospitals Leuven, the injections are followed by a period of bilateral stretching casts if indicated (below the knee walking casts and removable knee extension casts when necessary). All children will then undergo an intensive physical therapy program lasting 8-10 weeks. This post-BoNT therapy phase is guided by individualized treatment goals, which are established based on baseline assessments. These goals are determined during a multidisciplinary meeting with the treating physician, held prior to the BoNT injections. Thus, the intervention consists of BoNT treatment combined with an 8-10 week period of intensive physical therapy tailored to each child's specific therapeutic needs.

Primary

Change in the Spatial-temporal Parameter "Cadence".

Estimation of the cadence by three-dimensional gait analysis.

Control group: 3DGA was not performed

Posted

Median

Inter-Quartile Range

Number of steps/second

Between baseline and 8-10 weeks after the BoNT injections

ID	Title	Description
OG000	Intervention Group	The children in the intervention group will receive BoNT injections in the medial gastrocnemius and/or the semitendinosus muscle(s). As part of the standard treatment approach of the CP Reference Centre of the University Hospitals Leuven, the injections are followed by a period of bilateral stretching casts if indicated (below the knee walking casts and removable knee extension casts when necessary). All children will then undergo an intensive physical therapy program lasting 8-10 weeks. This post-BoNT therapy phase is guided by individualized treatment goals, which are established based on baseline assessments. These goals are determined during a multidisciplinary meeting with the treating physician, held prior to the BoNT injections. Thus, the intervention consists of BoNT treatment combined with an 8-10 week period of intensive physical therapy tailored to each child's specific therapeutic needs.
OG001	Control Group	This group will continue their usual care or normal routine treatment, i.e. physiotherapy and orthotic management during a period of 8-10 weeks.

Primary

Change in the Spatial-temporal Parameter "Walking Velocity".

Estimation of the walking velocity by three-dimensional gait analysis.

Control group: 3DGA was not performed

Posted

Median

Inter-Quartile Range

Meter/second

Between baseline and 8-10 weeks after the BoNT injections

ID	Title	Description
OG000	Intervention Group	The children in the intervention group will receive BoNT injections in the medial gastrocnemius and/or the semitendinosus muscle(s). As part of the standard treatment approach of the CP Reference Centre of the University Hospitals Leuven, the injections are followed by a period of bilateral stretching casts if indicated (below the knee walking casts and removable knee extension casts when necessary). All children will then undergo an intensive physical therapy program lasting 8-10 weeks. This post-BoNT therapy phase is guided by individualized treatment goals, which are established based on baseline assessments. These goals are determined during a multidisciplinary meeting with the treating physician, held prior to the BoNT injections. Thus, the intervention consists of BoNT treatment combined with an 8-10 week period of intensive physical therapy tailored to each child's specific therapeutic needs.
OG001	Control Group	This group will continue their usual care or normal routine treatment, i.e. physiotherapy and orthotic management during a period of 8-10 weeks.

Primary

Change in the Spatial-temporal Parameter "Stride Length".

Estimation of the stride length by three-dimensional gait analysis.

Control group: 3DGA was not performed

Posted

Median

Inter-Quartile Range

Meters

Between baseline and 8-10 weeks after the BoNT injections

ID	Title	Description
OG000	Intervention Group	The children in the intervention group will receive BoNT injections in the medial gastrocnemius and/or the semitendinosus muscle(s). As part of the standard treatment approach of the CP Reference Centre of the University Hospitals Leuven, the injections are followed by a period of bilateral stretching casts if indicated (below the knee walking casts and removable knee extension casts when necessary). All children will then undergo an intensive physical therapy program lasting 8-10 weeks. This post-BoNT therapy phase is guided by individualized treatment goals, which are established based on baseline assessments. These goals are determined during a multidisciplinary meeting with the treating physician, held prior to the BoNT injections. Thus, the intervention consists of BoNT treatment combined with an 8-10 week period of intensive physical therapy tailored to each child's specific therapeutic needs.
OG001	Control Group	This group will continue their usual care or normal routine treatment, i.e. physiotherapy and orthotic management during a period of 8-10 weeks.

Primary

Change in Spasticity of the Medial Gastrocnemius and the Medial Hamstrings

Muscle activity of the medial gastrocnemius and the medial hamstrings as recorded by surface electromyography (millivolts) during a passive stretch at high velocity of the plantar flexors and the hamstrings.

Control group: ISA was not performed n (medial hamstrings) = 13 < 14 due to insufficient cooperation

Posted

Median

Inter-Quartile Range

µV

Between baseline and 8-10 weeks after the BoNT injections

ID	Title	Description
OG000	Intervention Group	The children in the intervention group will receive BoNT injections in the medial gastrocnemius and/or the semitendinosus muscle(s). As part of the standard treatment approach of the CP Reference Centre of the University Hospitals Leuven, the injections are followed by a period of bilateral stretching casts if indicated (below the knee walking casts and removable knee extension casts when necessary). All children will then undergo an intensive physical therapy program lasting 8-10 weeks. This post-BoNT therapy phase is guided by individualized treatment goals, which are established based on baseline assessments. These goals are determined during a multidisciplinary meeting with the treating physician, held prior to the BoNT injections. Thus, the intervention consists of BoNT treatment combined with an 8-10 week period of intensive physical therapy tailored to each child's specific therapeutic needs.
OG001	Control Group

Secondary

Change in Normalized Muscle Tendon Unit Length of the Medial Gastrocnemius

Estimation of the muscle tendon unit length by three-dimensional freehand ultrasonography, expressed as a percentage of total leg length.

Posted

Median

Inter-Quartile Range

a percentage of total leg length

Between baseline and 8-10 weeks after the BoNT injections for the intervention group, and between baseline and 8-10 weeks later for the control group.

ID	Title	Description
OG000	Intervention Group	The children in the intervention group will receive BoNT injections in the medial gastrocnemius and/or the semitendinosus muscle(s). As part of the standard treatment approach of the CP Reference Centre of the University Hospitals Leuven, the injections are followed by a period of bilateral stretching casts if indicated (below the knee walking casts and removable knee extension casts when necessary). All children will then undergo an intensive physical therapy program lasting 8-10 weeks. This post-BoNT therapy phase is guided by individualized treatment goals, which are established based on baseline assessments. These goals are determined during a multidisciplinary meeting with the treating physician, held prior to the BoNT injections. Thus, the intervention consists of BoNT treatment combined with an 8-10 week period of intensive physical therapy tailored to each child's specific therapeutic needs.
OG001	Control Group	This group will continue their usual care or normal routine treatment, i.e. physiotherapy and orthotic management during a period of 8-10 weeks.

Secondary

Change in Normalized Muscle Belly Length of the Medial Gastrocnemius and the Distal Compartment of the Semitendinosus

Estimation of the muscle belly length by three-dimensional freehand ultrasonography, expressed as a percentage of total leg length.

Semitendinosus:

Intervention group: n = 24 < 25 due to bad quality data Control group: n = 19 < 20 due to bad quality data

Posted

Median

Inter-Quartile Range

a percentage of total leg length

Between baseline and 8-10 weeks after the BoNT injections for the intervention group, and between baseline and 8-10 weeks later for the control group.

ID	Title	Description
OG000	Intervention Group	The children in the intervention group will receive BoNT injections in the medial gastrocnemius and/or the semitendinosus muscle(s). As part of the standard treatment approach of the CP Reference Centre of the University Hospitals Leuven, the injections are followed by a period of bilateral stretching casts if indicated (below the knee walking casts and removable knee extension casts when necessary). All children will then undergo an intensive physical therapy program lasting 8-10 weeks. This post-BoNT therapy phase is guided by individualized treatment goals, which are established based on baseline assessments. These goals are determined during a multidisciplinary meeting with the treating physician, held prior to the BoNT injections. Thus, the intervention consists of BoNT treatment combined with an 8-10 week period of intensive physical therapy tailored to each child's specific therapeutic needs.
OG001

Secondary

Change in Normalized Tendon Length of the Medial Gastrocnemius

Estimation of the tendon length by three-dimensional freehand ultrasonography, expressed as a percentage of total leg length.

Posted

Median

Inter-Quartile Range

a percentage of total leg length

Between baseline and 8-10 weeks after the BoNT injections for the intervention group, and between baseline and 8-10 weeks later for the control group.

ID	Title	Description
OG000	Intervention Group	The children in the intervention group will receive BoNT injections in the medial gastrocnemius and/or the semitendinosus muscle(s). As part of the standard treatment approach of the CP Reference Centre of the University Hospitals Leuven, the injections are followed by a period of bilateral stretching casts if indicated (below the knee walking casts and removable knee extension casts when necessary). All children will then undergo an intensive physical therapy program lasting 8-10 weeks. This post-BoNT therapy phase is guided by individualized treatment goals, which are established based on baseline assessments. These goals are determined during a multidisciplinary meeting with the treating physician, held prior to the BoNT injections. Thus, the intervention consists of BoNT treatment combined with an 8-10 week period of intensive physical therapy tailored to each child's specific therapeutic needs.
OG001	Control Group	This group will continue their usual care or normal routine treatment, i.e. physiotherapy and orthotic management during a period of 8-10 weeks.

Secondary

Normalized Muscle Volume Growth Rates of the Medial Gastrocnemius and the Distal Compartment of the Semitendinosus

Estimation of the normalized muscle volume growth rates, calculated by (Normalized muscle volume (mL/kg*m)post-Normalized muscle volume pre (mL/kg*m))/(age (months)post-age (months)pre)

Semitendinosus:

Intervention group: n = 24 < 25 due to bad quality data Control group: n = 19 < 20 due to bad quality data

Posted

Median

Inter-Quartile Range

ml/kg*m/month

Between baseline and 8-10 weeks after the BoNT injections for the intervention group, and between baseline and 8-10 weeks later for the control group.

ID	Title	Description
OG000	Intervention Group	The children in the intervention group will receive BoNT injections in the medial gastrocnemius and/or the semitendinosus muscle(s). As part of the standard treatment approach of the CP Reference Centre of the University Hospitals Leuven, the injections are followed by a period of bilateral stretching casts if indicated (below the knee walking casts and removable knee extension casts when necessary). All children will then undergo an intensive physical therapy program lasting 8-10 weeks. This post-BoNT therapy phase is guided by individualized treatment goals, which are established based on baseline assessments. These goals are determined during a multidisciplinary meeting with the treating physician, held prior to the BoNT injections. Thus, the intervention consists of BoNT treatment combined with an 8-10 week period of intensive physical therapy tailored to each child's specific therapeutic needs.
OG001

Secondary

Change in the Kinematic Parameter "Ankle Range of Motion in Sagittal Plane During Stance Phase"

Estimation of ankle range of motion in sagittal plane during stance phase by three-dimensional gait analysis.

Control group: 3DGA was not performed

Posted

Median

Inter-Quartile Range

Degrees

Between baseline and 8-10 weeks after the BoNT injections

ID	Title	Description
OG000	Intervention Group	The children in the intervention group will receive BoNT injections in the medial gastrocnemius and/or the semitendinosus muscle(s). As part of the standard treatment approach of the CP Reference Centre of the University Hospitals Leuven, the injections are followed by a period of bilateral stretching casts if indicated (below the knee walking casts and removable knee extension casts when necessary). All children will then undergo an intensive physical therapy program lasting 8-10 weeks. This post-BoNT therapy phase is guided by individualized treatment goals, which are established based on baseline assessments. These goals are determined during a multidisciplinary meeting with the treating physician, held prior to the BoNT injections. Thus, the intervention consists of BoNT treatment combined with an 8-10 week period of intensive physical therapy tailored to each child's specific therapeutic needs.
OG001	Control Group	This group will continue their usual care or normal routine treatment, i.e. physiotherapy and orthotic management during a period of 8-10 weeks.

Secondary

Change in the Kinematic Parameter "Knee Range of Motion in Sagittal Plane During Stance Phase"

Estimation of knee range of motion in sagittal plane during stance phase by three-dimensional gait analysis.

Control group: 3DGA was not performed

Posted

Median

Inter-Quartile Range

Degrees

Between baseline and 8-10 weeks after the BoNT injections

ID	Title	Description
OG000	Intervention Group	The children in the intervention group will receive BoNT injections in the medial gastrocnemius and/or the semitendinosus muscle(s). As part of the standard treatment approach of the CP Reference Centre of the University Hospitals Leuven, the injections are followed by a period of bilateral stretching casts if indicated (below the knee walking casts and removable knee extension casts when necessary). All children will then undergo an intensive physical therapy program lasting 8-10 weeks. This post-BoNT therapy phase is guided by individualized treatment goals, which are established based on baseline assessments. These goals are determined during a multidisciplinary meeting with the treating physician, held prior to the BoNT injections. Thus, the intervention consists of BoNT treatment combined with an 8-10 week period of intensive physical therapy tailored to each child's specific therapeutic needs.
OG001	Control Group	This group will continue their usual care or normal routine treatment, i.e. physiotherapy and orthotic management during a period of 8-10 weeks.

Secondary

Change in Muscle Activation of the Medial Gastrocnemius and the Medial Hamstrings (i.e. the Change During the High-velocity Stretch).

Calculated by subtracting the muscle activation during a low-velocity stretch. Muscle activity of the medial gastrocnemius and Medial Hamstrings is recorded by surface electromyography (millivolts) during a passive stretch of the plantar flexors and of the hamstrings.

Control group: ISA was not performed n (medial hamstrings) = 13 < 14 due to insufficient cooperation

Posted

Median

Inter-Quartile Range

µV

Between baseline and 8-10 weeks after the BoNT injections

ID	Title	Description
OG000	Intervention Group	The children in the intervention group will receive BoNT injections in the medial gastrocnemius and/or the semitendinosus muscle(s). As part of the standard treatment approach of the CP Reference Centre of the University Hospitals Leuven, the injections are followed by a period of bilateral stretching casts if indicated (below the knee walking casts and removable knee extension casts when necessary). All children will then undergo an intensive physical therapy program lasting 8-10 weeks. This post-BoNT therapy phase is guided by individualized treatment goals, which are established based on baseline assessments. These goals are determined during a multidisciplinary meeting with the treating physician, held prior to the BoNT injections. Thus, the intervention consists of BoNT treatment combined with an 8-10 week period of intensive physical therapy tailored to each child's specific therapeutic needs.
OG001

Secondary

Change of Range of Motion in the Ankle and Knee Joint

Evaluation by goniometry expressed in degrees. For the ankle plantar flexion range of motion with the knee extended, for the hamstrings unilateral popliteal angle.

A standardized clinical examination was performed during the pre- and post-BoNT-A assessments of the intervention group and during the pre-assessment of the control group. These data were used to describe and compare both groups at baseline.

Posted

Median

Inter-Quartile Range

Degrees

Between baseline and 8-10 weeks after the BoNT injections

ID	Title	Description
OG000	Intervention Group	The children in the intervention group will receive BoNT injections in the medial gastrocnemius and/or the semitendinosus muscle(s). As part of the standard treatment approach of the CP Reference Centre of the University Hospitals Leuven, the injections are followed by a period of bilateral stretching casts if indicated (below the knee walking casts and removable knee extension casts when necessary). All children will then undergo an intensive physical therapy program lasting 8-10 weeks. This post-BoNT therapy phase is guided by individualized treatment goals, which are established based on baseline assessments. These goals are determined during a multidisciplinary meeting with the treating physician, held prior to the BoNT injections. Thus, the intervention consists of BoNT treatment combined with an 8-10 week period of intensive physical therapy tailored to each child's specific therapeutic needs.
OG001	Control Group

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Intervention Group	The children in the intervention group will receive BoNT injections in the medial gastrocnemius and/or the semitendinosus muscle(s). As part of the standard treatment approach of the CP Reference Centre of the University Hospitals Leuven, the injections are followed by a period of bilateral stretching casts if indicated (below the knee walking casts and removable knee extension casts when necessary). All children will then undergo an intensive physical therapy program lasting 8-10 weeks. This post-BoNT therapy phase is guided by individualized treatment goals, which are established based on baseline assessments. These goals are determined during a multidisciplinary meeting with the treating physician, held prior to the BoNT injections. Thus, the intervention consists of BoNT treatment combined with an 8-10 week period of intensive physical therapy tailored to each child's specific therapeutic needs.	0	25	0	25	0	25
EG001	Control Group	This group will continue their usual care or normal routine treatment, i.e. physiotherapy and orthotic management during a period of 8-10 weeks.	0	20	0	20	0	20

ID	Term
D002547	Cerebral Palsy
D009128	Muscle Spasticity

ID	Term
D001925	Brain Damage, Chronic
D001927	Brain Diseases
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases
D009135	Muscular Diseases
D009140	Musculoskeletal Diseases
D009122	Muscle Hypertonia
D020879	Neuromuscular Manifestations
D009461	Neurologic Manifestations
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms