Short Term Follow-up of a Botulinum Toxin Intervention in Children With Spastic Cerebral Palsy

NCT05126693 | Completed Results

• 1 other identifier: S59945_C
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Spastic Cerebral Palsy

Keywords

Cerebral Palsy; Spastic Cerebral Palsy; Botulinum Toxin; muscle morphology; Range of motion; Stiffness; Spasticity; Intensive physical therapy

Outcome Measures

Primary Outcomes (9)

• 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.

  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.

  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.

  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.

  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.

  Between baseline and 8-10 weeks after the BoNT injections

Secondary Outcomes (8)

• Change in Normalized Muscle Tendon Unit Length of the Medial Gastrocnemius

  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

  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

  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

  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"

  Between baseline and 8-10 weeks after the BoNT injections

Study Arms (2)

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

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).

Intervention group

Eligibility Criteria

• Age: 4 Years - 11 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Confirmed diagnosis of spastic cerebral palsy
• Aged 4-11 years
• GMFCS levels I-III (GMFCS = Gross Motor Function Classification Score, expressing the overall functional level of impairment)
• Sufficient cooperation to comprehend and complete the test procedure

You may not qualify if:

• Non-ambulatory
• Botulinum toxin A injections six months prior to enrollment
• Lower limb surgery two years prior to enrollment
• Previous selective dorsal rhizotomy
• Presence of ataxia or dystonia
• Cognitive problems that impede measurements
• Severe co-morbidities (severe epilepsy, non-correctable visual impairment, autism spectrum disorders, mental problems that prevent comprehensiveness of the tasks)
• Hospitalization after the BoNT treatment for intensive physical therapy
• Intrathecal baclofen pump
• For the control group: new intervention planned within 3 months

Sponsors & Collaborators

• Universitaire Ziekenhuizen KU Leuven: lead
• KU Leuven: collaborator

Study Sites (1)

UZ Leuven

Leuven, Vlaams-Brabant, 3000, Belgium

Location

Related Publications (11)

• 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.

  PMID: 23791154 BACKGROUND

• Bar-On L, Van Campenhout A, Desloovere K, Aertbelien E, Huenaerts C, Vandendoorent B, Nieuwenhuys A, Molenaers G. Is an instrumented spasticity assessment an improvement over clinical spasticity scales in assessing and predicting the response to integrated botulinum toxin type a treatment in children with cerebral palsy? Arch Phys Med Rehabil. 2014 Mar;95(3):515-23. doi: 10.1016/j.apmr.2013.08.010. Epub 2013 Aug 27.

  PMID: 23994052 BACKGROUND

• Franki I, Bar-On L, Molenaers G, Van Campenhout A, Craenen K, Desloovere K, Feys H, Pauwels P, De Cat J, Ortibus E. Tone Reduction and Physical Therapy: Strengthening Partners in Treatment of Children with Spastic Cerebral Palsy. Neuropediatrics. 2020 Apr;51(2):89-104. doi: 10.1055/s-0039-3400987. Epub 2019 Nov 27.

  PMID: 31777043 BACKGROUND

• Franki I, Desloovere K, De Cat J, Feys H, Molenaers G, Calders P, Vanderstraeten G, Himpens E, Van Broeck C. The evidence-base for basic physical therapy techniques targeting lower limb function in children with cerebral palsy: a systematic review using the International Classification of Functioning, Disability and Health as a conceptual framework. J Rehabil Med. 2012 May;44(5):385-95. doi: 10.2340/16501977-0983.

  PMID: 22549646 BACKGROUND

• Molenaers G, Fagard K, Van Campenhout A, Desloovere K. Botulinum toxin A treatment of the lower extremities in children with cerebral palsy. J Child Orthop. 2013 Nov;7(5):383-7. doi: 10.1007/s11832-013-0511-x. Epub 2013 Aug 28.

  PMID: 24432099 BACKGROUND

• Peeters N, Van Campenhout A, Hanssen B, Cenni F, Schless SH, Van den Broeck C, Desloovere K, Bar-On L. Joint and Muscle Assessments of the Separate Effects of Botulinum NeuroToxin-A and Lower-Leg Casting in Children With Cerebral Palsy. Front Neurol. 2020 Apr 21;11:210. doi: 10.3389/fneur.2020.00210. eCollection 2020.

  PMID: 32373040 BACKGROUND

• Cenni F, Monari D, Desloovere K, Aertbelien E, Schless SH, Bruyninckx H. The reliability and validity of a clinical 3D freehand ultrasound system. Comput Methods Programs Biomed. 2016 Nov;136:179-87. doi: 10.1016/j.cmpb.2016.09.001. Epub 2016 Sep 6.

  PMID: 27686714 BACKGROUND

• Bar-On L, Aertbelien E, Wambacq H, Severijns D, Lambrecht K, Dan B, Huenaerts C, Bruyninckx H, Janssens L, Van Gestel L, Jaspers E, Molenaers G, Desloovere K. A clinical measurement to quantify spasticity in children with cerebral palsy by integration of multidimensional signals. Gait Posture. 2013 May;38(1):141-7. doi: 10.1016/j.gaitpost.2012.11.003. Epub 2012 Dec 4.

  PMID: 23218728 BACKGROUND

• Molenaers, G., Desloovere, K., Eyssen, M., Decaf, J., Jonkers, I., & Cock, P. De. (1999). Botulinum toxin type A treatment of cerebral palsy: an integrated approach. European Journal of Neurology, 6, s51-s57. https://doi.org/10.1111/j.1468-1331.1999.tb00035.x

  BACKGROUND

• Peeters N, Papageorgiou E, Hanssen B, De Beukelaer N, Staut L, Degelaen M, Van den Broeck C, Calders P, Feys H, Van Campenhout A, Desloovere K. The Short-Term Impact of Botulinum Neurotoxin-A on Muscle Morphology and Gait in Children with Spastic Cerebral Palsy. Toxins (Basel). 2022 Sep 29;14(10):676. doi: 10.3390/toxins14100676.

  PMID: 36287944 RESULT

• Peeters N, Hanssen B, Bar-On L, De Groote F, De Beukelaer N, Coremans M, Van den Broeck C, Dan B, Van Campenhout A, Desloovere K. Associations between muscle morphology and spasticity in children with spastic cerebral palsy. Eur J Paediatr Neurol. 2023 May;44:1-8. doi: 10.1016/j.ejpn.2023.01.007. Epub 2023 Jan 10.

  PMID: 36706682 RESULT

MeSH Terms

Conditions

Cerebral Palsy; Muscle Spasticity

Condition Hierarchy (Ancestors)

Brain Damage, Chronic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Muscular Diseases; Musculoskeletal Diseases; Muscle Hypertonia; Neuromuscular Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Prof. dr. Kaat Desloovere
• Organization: KU Leuven

kaat.desloovere@kuleuven.be

+32 486 40 13 73

Study Officials

• Kaat Desloovere, Prof. Dr.

  UZ Leuven

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr.

Model Details: We will include patients who receive BoNT injections at the lower limb in the intervention group. Patient with no indication for treatment in the next three months (besides the routine physical therapy and orthotic management) will be asked to participate in the control group. Justification for the non-randomized design is stated above.

Study Record Dates

• First Submitted: August 17, 2021
• First Posted: November 19, 2021
• Study Start: August 3, 2020
• Primary Completion: May 10, 2022
• Study Completion: May 10, 2022
• Last Updated: July 31, 2025
• Results First Posted: July 31, 2025

Record last verified: 2025-05

Locations

BE (1)