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

Spastic Cerebral Palsy Clinical Trial

Official title:

Algorithms for Patient-specific Treatment Planning in Cerebral Palsy Based on the Muscle and Tendon Architecture - Short Term Follow-up of a Botulinum Toxin Intervention in Children With Spastic Cerebral Palsy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05126693
• Other study ID #: S59945_C
• Status: Completed
• Phase: N/A
• Start date: August 3, 2020
• Est. completion date: May 10, 2022

Study information

• Verified date: March 2024
• Source: Universitaire Ziekenhuizen KU Leuven
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: May 10, 2022
• Est. primary completion date: May 10, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 4 Years to 11 Years

Eligibility

Inclusion Criteria:

• 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

• Additional exclusion criterion for the intervention group specifically: Indication for BoNT injections

Exclusion Criteria:

• 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

• Additional exclusion criterion for the control group specifically: new intervention planned within 3 months

Related Conditions & MeSH terms

• Cerebral Palsy
• Muscle Spasticity
• Paralysis
• Spastic Cerebral Palsy

Intervention

Other:
• Botulinum Toxin treatment combined with a post-BoNT intensive physical therapy period guided by individualized treatment goals.
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).

Locations

Country	Name	City	State
Belgium	UZ Leuven	Leuven	Vlaams-Brabant

Sponsors (2)

Lead Sponsor	Collaborator
Universitaire Ziekenhuizen KU Leuven	KU Leuven

Country where clinical trial is conducted

Belgium, 

References & 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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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

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 Ma — View Citation

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 — View Citation

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. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Compliance of the treatment goals during intensive physical therapy period	During telephone interviews every two weeks with the physical therapist, the compliance to the physical therapy with individual goals is assessed.	Every two weeks during the 8-10 weeks of intensive physical therapy after the BoNT injections
Primary	Change in muscle volume medial gastrocnemius and semitendinosus.	Estimation of the muscle belly volume by 3D freehand ultrasonography	Between baseline and 8-10 weeks after the BoNT treatment
Primary	Change in spasticity of the medial gastrocnemius and medial hamstrings	Muscle activity of the medial gastrocnemius or medial hamstrings is recorded by surface electromyography (EMG) (millivolts) during a passive stretch of the plantar flexors or hamstrings respectively	Between baseline and 8-10 weeks after the BoNT treatment
Secondary	Change in echo-intensity of the medial gastrocnemius and medial hamstrings	Estimation of the echo-intensity by 3D freehand ultrasonography.	Between baseline and 8-10 weeks after the BoNT injections
Secondary	Change in muscle belly and tendon length of the medial gastrocnemius and medial hamstrings	Estimation of the muscle and tendon length by 3D freehand ultrasonography.	Between baseline and 8-10 weeks after the BoNT injections
Secondary	Change in stiffness of the ankle and knee joint	Stiffness is assessed by estimating the resistance (torque at a specific joint angle or work over the ROM) at the ankle or knee joint during a slow passive stretch	Between baseline and 8-10 weeks after the BoNT injections
Secondary	Change in functional pre-defined goals	Change in functional pre-defined treatment goals, attained by the goal attainment scale (GAS) score (from -2 to +2).	Between baseline and 8-10 weeks after the BoNT injections
Secondary	Change in functional muscle strength	Evaluation of functional muscle strength by the Adapted Functional Strength measure.	Between baseline and 8-10 weeks after the BoNT injections
Secondary	Change of Range of motion in the ankle and knee joint	ROM is measured by initial measurement units (IMU's) that are attached to the different segments. The joint angle (degrees) is calculate as the difference in position between two IMU's	Between baseline and 8-10 weeks after the BoNT injections
Secondary	Change of Range of motion in the ankle and knee joint	Evaluation by goniometry expressed in degrees	Between baseline and 8-10 weeks after the BoNT injections