Clinical trial NCT05126693: Short Term Follow-up of a Botulinum Toxin Intervention in Children With Spastic Cerebral Palsy
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Spastic Cerebral Palsy
Keywords: Cerebral Palsy
Spastic Cerebral Palsy
Botulinum Toxin
muscle morphology
Range of motion
Stiffness
Spasticity
Intensive physical therapy
Lead sponsor: Universitaire Ziekenhuizen KU Leuven
Sponsor class: OTHER
Collaborators: name: KU Leuven
First posted: 2021-11-19
Enrollment: 45
Sex: ALL
Minimum age (years): 4
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in muscle volume medial gastrocnemius and semitendinosus.
timeFrame: Between baseline and 8-10 weeks after the BoNT treatment
measure: Change in spasticity of the medial gastrocnemius and medial hamstrings
timeFrame: Between baseline and 8-10 weeks after the BoNT treatment
Secondary outcomes:
measure: Change in echo-intensity of the medial gastrocnemius and medial hamstrings
timeFrame: Between baseline and 8-10 weeks after the BoNT injections
measure: Change in muscle belly and tendon length of the medial gastrocnemius and medial hamstrings
timeFrame: Between baseline and 8-10 weeks after the BoNT injections
measure: Change in stiffness of the ankle and knee joint
timeFrame: Between baseline and 8-10 weeks after the BoNT injections
measure: Change in functional pre-defined goals
timeFrame: Between baseline and 8-10 weeks after the BoNT injections
measure: Change in functional muscle strength
timeFrame: Between baseline and 8-10 weeks after the BoNT injections
measure: Change of Range of motion in the ankle and knee joint
timeFrame: Between baseline and 8-10 weeks after the BoNT injections
measure: Change of Range of motion in the ankle and knee joint
timeFrame: Between baseline and 8-10 weeks after the BoNT injections
Other outcomes:
measure: Compliance of the treatment goals during intensive physical therapy period
timeFrame: Every two weeks during the 8-10 weeks of intensive physical therapy after the BoNT injections
Locations:
city: Leuven
country: Belgium
facility: UZ Leuven
state: Vlaams-Brabant
Study officials:
affiliation: UZ Leuven
name: Kaat Desloovere, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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.
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