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

Primary Purpose

Spastic Cerebral Palsy

Status
Recruiting
Phase
Not Applicable
Locations
Belgium
Study Type
Interventional
Intervention
Botulinum Toxin treatment combined with a post-BoNT intensive physical therapy period guided by individualized treatment goals.
Sponsored by
Universitaire Ziekenhuizen KU Leuven
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Spastic Cerebral Palsy focused on measuring Cerebral Palsy, Spastic Cerebral Palsy, Botulinum Toxin, muscle morphology, Range of motion, Stiffness, Spasticity, Intensive physical therapy

Eligibility Criteria

4 Years - 11 Years (Child)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • UZ LeuvenRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Intervention group

Control group

Arm Description

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).

This group will continue their usual care or normal routine treatment, i.e. physiotherapy and orthotic management during a period of 8-10 weeks.

Outcomes

Primary Outcome Measures

Change in muscle volume medial gastrocnemius and semitendinosus.
Estimation of the muscle belly volume by 3D freehand ultrasonography
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

Secondary Outcome Measures

Change in echo-intensity of the medial gastrocnemius and medial hamstrings
Estimation of the echo-intensity by 3D freehand ultrasonography.
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.
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
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).
Change in functional muscle strength
Evaluation of functional muscle strength by the Adapted Functional Strength measure.
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
Change of Range of motion in the ankle and knee joint
Evaluation by goniometry expressed in degrees

Full Information

First Posted
August 17, 2021
Last Updated
November 17, 2021
Sponsor
Universitaire Ziekenhuizen KU Leuven
Collaborators
KU Leuven
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1. Study Identification

Unique Protocol Identification Number
NCT05126693
Brief Title
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

2. Study Status

Record Verification Date
November 2021
Overall Recruitment Status
Recruiting
Study Start Date
August 3, 2020 (Actual)
Primary Completion Date
August 2022 (Anticipated)
Study Completion Date
August 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Universitaire Ziekenhuizen KU Leuven
Collaborators
KU Leuven

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Spastic Cerebral Palsy
Keywords
Cerebral Palsy, Spastic Cerebral Palsy, Botulinum Toxin, muscle morphology, Range of motion, Stiffness, Spasticity, Intensive physical therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
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.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Intervention group
Arm Type
Experimental
Arm Description
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).
Arm Title
Control group
Arm Type
No Intervention
Arm Description
This group will continue their usual care or normal routine treatment, i.e. physiotherapy and orthotic management during a period of 8-10 weeks.
Intervention Type
Other
Intervention Name(s)
Botulinum Toxin treatment combined with a post-BoNT intensive physical therapy period guided by individualized treatment goals.
Intervention Description
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).
Primary Outcome Measure Information:
Title
Change in muscle volume medial gastrocnemius and semitendinosus.
Description
Estimation of the muscle belly volume by 3D freehand ultrasonography
Time Frame
Between baseline and 8-10 weeks after the BoNT treatment
Title
Change in spasticity of the medial gastrocnemius and medial hamstrings
Description
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
Time Frame
Between baseline and 8-10 weeks after the BoNT treatment
Secondary Outcome Measure Information:
Title
Change in echo-intensity of the medial gastrocnemius and medial hamstrings
Description
Estimation of the echo-intensity by 3D freehand ultrasonography.
Time Frame
Between baseline and 8-10 weeks after the BoNT injections
Title
Change in muscle belly and tendon length of the medial gastrocnemius and medial hamstrings
Description
Estimation of the muscle and tendon length by 3D freehand ultrasonography.
Time Frame
Between baseline and 8-10 weeks after the BoNT injections
Title
Change in stiffness of the ankle and knee joint
Description
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
Time Frame
Between baseline and 8-10 weeks after the BoNT injections
Title
Change in functional pre-defined goals
Description
Change in functional pre-defined treatment goals, attained by the goal attainment scale (GAS) score (from -2 to +2).
Time Frame
Between baseline and 8-10 weeks after the BoNT injections
Title
Change in functional muscle strength
Description
Evaluation of functional muscle strength by the Adapted Functional Strength measure.
Time Frame
Between baseline and 8-10 weeks after the BoNT injections
Title
Change of Range of motion in the ankle and knee joint
Description
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
Time Frame
Between baseline and 8-10 weeks after the BoNT injections
Title
Change of Range of motion in the ankle and knee joint
Description
Evaluation by goniometry expressed in degrees
Time Frame
Between baseline and 8-10 weeks after the BoNT injections
Other Pre-specified Outcome Measures:
Title
Compliance of the treatment goals during intensive physical therapy period
Description
During telephone interviews every two weeks with the physical therapist, the compliance to the physical therapy with individual goals is assessed.
Time Frame
Every two weeks during the 8-10 weeks of intensive physical therapy after the BoNT injections

10. Eligibility

Sex
All
Minimum Age & Unit of Time
4 Years
Maximum Age & Unit of Time
11 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Nicky Peeters
Phone
+3216341016
Email
nicky.peeters@kuleuven.be
First Name & Middle Initial & Last Name or Official Title & Degree
Julie Uytterhoeven
Email
julie.uytterhoeven@kuleuven.be
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kaat Desloovere, Prof. Dr.
Organizational Affiliation
UZ Leuven
Official's Role
Principal Investigator
Facility Information:
Facility Name
UZ Leuven
City
Leuven
State/Province
Vlaams-Brabant
ZIP/Postal Code
3000
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kaat Desloovere, Prof. Dr.
Phone
+3216338009
Email
kaat.desloovere@kuleuven.be

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
23791154
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.
Results Reference
background
PubMed Identifier
23994052
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.
Results Reference
background
PubMed Identifier
31777043
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.
Results Reference
background
PubMed Identifier
22549646
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.
Results Reference
background
PubMed Identifier
24432099
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.
Results Reference
background
PubMed Identifier
32373040
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.
Results Reference
background
PubMed Identifier
27686714
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.
Results Reference
background
PubMed Identifier
23218728
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.
Results Reference
background
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
Results Reference
background

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

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