An interventional study of Botulinum Toxin treatment combined with a post-BoNT intensive physical therapy period guided by individualized treatment goals. in Spastic Cerebral Palsy, sponsored by Universitaire Ziekenhuizen KU Leuven. Completed at 1 site in Belgium. Open to participants aged 4 Years to 11 Years. Per ClinicalTrials.gov, last updated 2025-07-31.
Sponsored by Universitaire Ziekenhuizen KU Leuven · Not applicable, Interventional, and Treatment
This study investigates the effect of integrated Botulinum Neurotoxin A (BoNT) treatment on morphologic muscle and tendon properties, spasticity, joint stiffness, joint range of motion, muscle strength, gait and gross motor function. The integrated BoNT treatment combines BoNT-injections with serial casting and intensive physical therapy, as previously described by Molenaers et al. The current study will include 30 children who are clinically scheduled for BoNT treatment in the medial gastrocnemius and/or the semitendinosus muscle in the intervention group and 30 children in a control group who will receive usual care within a time span of 3 months.
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.
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Exclusion Criteria:
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.
This group will continue their usual care or normal routine treatment, i.e. physiotherapy and orthotic management during a period of 8-10 weeks.
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).
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
Time frame: 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.
Time frame: 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)
Time frame: 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.
Time frame: 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.
Time frame: Between baseline and 8-10 weeks after the BoNT injections
Change in the Spatial-temporal Parameter "Cadence".
Estimation of the cadence by three-dimensional gait analysis.
Time frame: Between baseline and 8-10 weeks after the BoNT injections
Change in the Spatial-temporal Parameter "Walking Velocity".
Estimation of the walking velocity by three-dimensional gait analysis.
Time frame: Between baseline and 8-10 weeks after the BoNT injections
Change in the Spatial-temporal Parameter "Stride Length".
Estimation of the stride length by three-dimensional gait analysis.
Time frame: Between baseline and 8-10 weeks after the BoNT injections
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.
Time frame: Between baseline and 8-10 weeks after the BoNT injections
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.
Time frame: 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 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.
Time frame: 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 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.
Time frame: 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.
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)
Time frame: 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 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.
Time frame: Between baseline and 8-10 weeks after the BoNT injections
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.
Time frame: Between baseline and 8-10 weeks after the BoNT injections
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.
Time frame: Between baseline and 8-10 weeks after the BoNT injections
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.
Time frame: Between baseline and 8-10 weeks after the BoNT injections
| Milestone | Intervention Group | Control Group |
|---|---|---|
| Started | 31 | 30 |
| Completed | 25 | 20 |
| Not completed | 6 | 10 |
| Withdrew: Bad 3dga data | 2 | 0 |
| Withdrew: No 3dga | 4 | 0 |
| Withdrew: Insufficient matching | 0 | 10 |
| Milestone | Intervention Group | Control Group |
|---|---|---|
| Started | 25 | 20 |
| Completed | 25 | 20 |
| Not completed | 0 | 0 |
Estimation of the muscle belly volume by three-dimensional freehand ultrasonography normalized to the product of body weight and height
| ml/kg*m | Intervention Group | Control Group |
|---|---|---|
| Medial Gastrocnemius | -0.08 (-0.16 to 0.04) | 0.00 (-0.09 to 0.06) |
| Semitendinosus | -0.09 (-0.16 to 0.01) | -0.01 (-0.07 to 0.04) |
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.
| Arbitrary units ranging from 0 to 255 | Intervention Group | Control Group |
|---|---|---|
| Medial Gastrocnemius | 2.74 (-5.63 to 11.11) | -0.08 (-3.77 to 9.33) |
| Semitendinosus | 6.58 (-8.27 to 16.61) | 5.20 (-6.90 to 11.90) |
Estimation of the absolute muscle volume growth rate, calculated by: (muscle volume (mL)post-muscle volume pre)/(age (months)post-age (months)pre)
| ml/month | Intervention Group | Control Group |
|---|---|---|
| Medial Gastrocnemius | 0.00 (-1.34 to 0.97) | 0.17 (-0.23 to 0.87) |
| Semitendinosus | -0.49 (-1.45 to 0.58) | 0.02 (-0.39 to 0.48) |
Estimation of the kinematic parameters throughout the whole gait cycle by three-dimensional gait analysis.
| Degrees | Intervention Group | Control Group |
|---|---|---|
| Ankle Range of Motion in Sagittal Plane | -1.74 (-9.04 to 3.07) | — |
| Ankle Angle in Sagittal Plane at Initial Contact | 3.56 (0.47 to 6.36) | — |
| Maximal Ankle Angle in Sagittal Plane During Stance Phase | 3.99 (-0.32 to 9.99) | — |
| Maximal Ankle Angle in Sagittal Plane During Swing Phase | 5.34 (1.16 to 9.70) | — |
| Knee Range of Motion in Sagittal Plane | 1.94 (-3.79 to 8.84) | — |
| Knee Angle in Sagittal Plane at Initial Contact | -1.69 (-9.19 to 1.84) | — |
| Minimal Knee Angle in Sagittal Plane During Stance | -2.44 (-7.61 to 2.23) | — |
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.
| Degrees | Intervention Group | Control Group |
|---|---|---|
| Change in Gait Profile Score (Degrees) | -1.76 (-2.51 to -0.15) | — |
Estimation of the cadence by three-dimensional gait analysis.
| Number of steps/second | Intervention Group | Control Group |
|---|---|---|
| Change in the Spatial-temporal Parameter "Cadence". | -0.05 (-0.28 to 0.10) | — |
Estimation of the walking velocity by three-dimensional gait analysis.
| Meter/second | Intervention Group | Control Group |
|---|---|---|
| Change in the Spatial-temporal Parameter "Walking Velocity". | 0.01 (-0.10 to 0.10) | — |
Estimation of the stride length by three-dimensional gait analysis.
| Meters | Intervention Group | Control Group |
|---|---|---|
| Change in the Spatial-temporal Parameter "Stride Length". | 0.02 (-0.03 to 0.08) | — |
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.
| µV | Intervention Group | Control Group |
|---|---|---|
| Medial Gastrocnemius | -4.73 (-15.74 to 1.31) | — |
| Medial Hamstrings | -2.82 (-7.64 to 0.21) | — |
Estimation of the muscle tendon unit length by three-dimensional freehand ultrasonography, expressed as a percentage of total leg length.
| a percentage of total leg length | Intervention Group | Control Group |
|---|---|---|
| Change in Normalized Muscle Tendon Unit Length of the Medial Gastrocnemius | 0.88 (-0.22 to 1.59) | -0.35 (-0.86 to 0.52) |
Estimation of the muscle belly length by three-dimensional freehand ultrasonography, expressed as a percentage of total leg length.
| a percentage of total leg length | Intervention Group | Control Group |
|---|---|---|
| Medial Gastrocnemius | 0.44 (0.03 to 1.25) | -0.13 (-0.92 to 0.71) |
| Semitendinosus | -0.32 (-0.90 to 1.47) | -0.22 (-0.74 to 0.83) |
Estimation of the tendon length by three-dimensional freehand ultrasonography, expressed as a percentage of total leg length.
| a percentage of total leg length | Intervention Group | Control Group |
|---|---|---|
| Change in Normalized Tendon Length of the Medial Gastrocnemius | -0.03 (-0.88 to 1.17) | -0.26 (-0.55 to 0.24) |
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)
| ml/kg*m/month | Intervention Group | Control Group |
|---|---|---|
| Medial Gastrocnemius | -0.02 (-0.07 to 0.03) | 0.01 (-0.04 to 0.02) |
| Semitendinosus | -0.02 (-0.08 to 0.01) | -0.00 (-0.03 to 0.02) |
Estimation of ankle range of motion in sagittal plane during stance phase by three-dimensional gait analysis.
| Degrees | Intervention Group | Control Group |
|---|---|---|
| Change in the Kinematic Parameter "Ankle Range of Motion in Sagittal Plane During Stance Phase" | 0.31 (-4.38 to 3.74) | — |
Estimation of knee range of motion in sagittal plane during stance phase by three-dimensional gait analysis.
| Degrees | Intervention Group | Control Group |
|---|---|---|
| Change in the Kinematic Parameter "Knee Range of Motion in Sagittal Plane During Stance Phase" | 3.68 (-0.43 to 6.91) | — |
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.
| µV | Intervention Group | Control Group |
|---|---|---|
| Medial Gastrocnemius | -2.64 (-8.06 to 2.48) | — |
| Medial Hamstrings | -3.13 (-5.78 to 0.87) | — |
Evaluation by goniometry expressed in degrees. For the ankle plantar flexion range of motion with the knee extended, for the hamstrings unilateral popliteal angle.
| Degrees | Intervention Group | Control Group |
|---|---|---|
| Plantar flexors | 0.0 (0.00 to 5.0) | — |
| Hamstrings | 0.0 (-0.5 to 1.3) | — |
Collected over 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.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Intervention Group | 0/25 (0%) | 0/25 (0%) | 0/25 (0%) |
| Control Group | 0/20 (0%) | 0/20 (0%) | 0/20 (0%) |
| Age, Categorical(Participants) | Intervention Group | Control Group | Total |
|---|---|---|---|
| <=18 years | 25 | 20 | 45 |
| Between 18 and 65 years | 0 | 0 | 0 |
| >=65 years | 0 | 0 | 0 |
| Age, Continuous(Years) | Intervention Group | Control Group | Total |
|---|---|---|---|
| Median | 6.4 (4.6 to 8.5) | 7.6 (6.2 to 9.4) | 7.1 (5.9 to 9.1) |
| Sex: Female, Male(Participants) | Intervention Group | Control Group | Total |
|---|---|---|---|
| Female | 12 | 4 | 16 |
| Male | 13 | 16 | 29 |
| Race and Ethnicity Not Collected(Participants) | Intervention Group | Control Group | Total |
|---|---|---|---|
| Count of participants | — | — | 0 |
| Region of Enrollment(participants) | Intervention Group | Control Group | Total |
|---|---|---|---|
| Belgium | 25 | 20 | 45 |
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Universitaire Ziekenhuizen KU Leuven