Influence of Immobilisation, Stretching and Activity on Morphological and Mechanical Properties of Spastic Muscle

Study Overview
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Brief Summary
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Neurologic changes caused by cerebral palsy (CP) result in adaptation of muscle architecture and function (e.g. shortened muscles and contractures). Stretching through immobilization (orthotic treatment) is one of the common interventions to bring the spastic muscle to growth. Positive outcomes of stretching through immobilization are increased range of motion and improved function. On the other hand, immobilization leads to disuse muscle atrophy. Hence, we hypothesize that combining a stretching through immobilization and muscle activity while controlling for foot deformity could be a superior treatment approach, which should lead to improved muscle morphology as well as function. The aim of the study is to examine the influence of two orthotic treatments (a standard regime and one new approach) on spastic plantar flexor muscles in children and adolescents with CP. The standard regime (stretching through immobilisation) includes a dynamic AFO (ankle-foot orthosis) used during day and night. The new approach combines stretching through immobilisation and allows for plantarflexor activity due to an innovative construction of the orthotic device. This prospective randomized controlled study will recruit 20 ambulant children and adolescents (aged 5 to 15 years) with cerebral palsy and equinus deformity (GMFCS = Gross Motor Function Classification System level I to III). Each child will be randomized and stratified according to age and GMFCS to one of two groups. The first group receives the standard treatment (stretching through immobilization) using custom-made ankle foot orthosis for 23 hours per day. The other group will be treated with the same orthosis at night (8 hours) and for 6 hours during the day but the remaining 10 hours will be treated with the foot shell only that corrects subtalar and Chopart joints but does not block the ankle joint movement, so that more activity of plantarflexors will be possible during the day. The intervention will last for 12 weeks. Each child will be examined at four occasions (8 weeks before intervention = control phase, at the beginning of the intervention and then 8 and 12 weeks later). The main outcome measure is the fascicle length measured using a 3D ultrasound (3DUS) imaging technique. Further parameters of interest span across the whole levels of ICF including clinical examinations, biomechanics of gait, muscle morphologic and mechanic properties and participations questionnaires.

Official Title
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Influence of Immobilisation, Stretching and Activity on Morphological and Mechanical Properties of Spastic Muscle

Conditions
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Cerebral Palsy, Spastic

Intervention / Treatment
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* Other: Stretching through immobilisation (IG)
* Other: Stretching through immobilisation and activity (IAG)
* Other: Control Phase


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ambulatory children with spastic CP. Ability to accept and follow verbal instruction. Limited range of motion in ankle joint - maximal dorsiflexion with knee extended ≤ 5° Gross Motor Functional Classification System level I-III. Age 5-15 years. Willingness to participate. Exclusion Criteria: Other than spastic form of CP (ataxic, athetoid or dystonic). Severe mental retardation. Normal range of motion in ankle joint Oral antispastic or muscle relaxing medication. History of orthopaedic surgery in the last 12 months. History of botulinum toxin type A application in the last six months.

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 15 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Immobilization group (IG)<br>One group - immobilization group (IG) - will receive the standard treatment. | Other: Stretching through immobilisation (IG)<br>* The immobilization group (IG) will receive the standard treatment, a dynamic ankle-foot orthosis (AFO) for night and day use (23 hours per day)<br>* Other names: IG;|
| Experimental: Immobilization/Activity Group (IAG)<br>The other group - Immobilization/Activity Group (IAG) - will be treated with a new approach. | Other: Stretching through immobilisation and activity (IAG)<br>* The Immobilization/Activity Group (IAG) will be treated with the same type of ankle-foot orthosis at night (8 hours) and for 6 hours during the day (altogether orthosis treatment 14 hours per day). The rest of the day (10 hours) children and adolescents will be using only the foot shell of orthoses (FS) without the lower leg shell, to secure the correct position of the foot and to allow a free motion at ankle joint with a good correction of the foot deformity (e.g. Pes equinovarus / equinovalgus, midfoot-break).<br>* Other names: IAG;|
| Other: Control Phase<br>Before the intervention with the orthotic treatment starts, a control phase of 8 weeks is planned. | Other: Control Phase<br>* Before the intervention with the orthotic treatment starts, a control phase of 8 weeks is planned. During this time, the individual orthoses for each subject are manufactured.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in mechano-morphological muscle-tendon properties - muscle volume | Gastrocnemius medialis muscle volume | Time Frame: baseline (T1), PRE-measurement (T2, 8 weeks), POST-measurement (T3, 16 weeks), FOLLOW-UP measurement (T4, 20 weeks) | 
| Change in mechano-morphological muscle-tendon properties - fascile length | Gastrocnemius medialis fascile length | Time Frame: baseline (T1), PRE-measurement (T2, 8 weeks), POST-measurement (T3, 16 weeks), FOLLOW-UP measurement (T4, 20 weeks) | 
| Change in mechano-morphological muscle-tendon properties - unit length | Gastrocnemius medialis muscle belly, tendon and muscle-tendon unit length | Time Frame: baseline (T1), PRE-measurement (T2, 8 weeks), POST-measurement (T3, 16 weeks), FOLLOW-UP measurement (T4, 20 weeks) | 
| Change in mechano-morphological muscle-tendon properties - elongation | Passive gastrocnemius medialis muscle belly, tendon and muscle-tendon unit elongation due to externally applied torque to the ankle joint [elongation in mm] | Time Frame: baseline (T1), PRE-measurement (T2, 8 weeks), POST-measurement (T3, 16 weeks), FOLLOW-UP measurement (T4, 20 weeks) | 
| Change in mechano-morphological muscle-tendon properties - stiffness | Passive gastrocnemius medialis muscle belly, tendon and muscle-tendon unit stiffness due to externally applied torque to the ankle joint [stiffness in N/mm] | Time Frame: baseline (T1), PRE-measurement (T2, 8 weeks), POST-measurement (T3, 16 weeks), FOLLOW-UP measurement (T4, 20 weeks) | 
| Change in joint range of motion | Ankle joint range of motion (maximal plantarflexion - maximal dorsiflexion) | Time Frame: baseline (T1), PRE-measurement (T2, 8 weeks), POST-measurement (T3, 16 weeks), FOLLOW-UP measurement (T4, 20 weeks) | 
| Change in maximal isometric muscle strength | Maximal isometric torque production (isokinetic dynamometry) | Time Frame: baseline (T1), PRE-measurement (T2, 8 weeks), POST-measurement (T3, 16 weeks), FOLLOW-UP measurement (T4, 20 weeks) | 
| Change in gait characteristics | Gait kinematics (joint angles [°]) and kinetics (joint moments [Nm/kg]) of the hip, knee, and ankle joints (3D motion capture). Joint angles [°] and moments [Nm/kg] will be combined to report changes in gait pattern. | Time Frame: baseline (T1), PRE-measurement (T2, 8 weeks), POST-measurement (T3, 16 weeks), FOLLOW-UP measurement (T4, 20 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in self-reported gait, mobility, and functional performance - GOAL | Gait Outcomes Assessment List (GOAL) Questionnaire | Time Frame: baseline (T1), PRE-measurement (T2, 8 weeks), POST-measurement (T3, 16 weeks), FOLLOW-UP measurement (T4, 20 weeks) | 
| Change in self-reported gait, mobility, and functional performance - PODCI | Pediatrics Outcomes Data Collection Instrument (PODCI) Questionnaire | Time Frame: baseline (T1), PRE-measurement (T2, 8 weeks), POST-measurement (T3, 16 weeks), FOLLOW-UP measurement (T4, 20 weeks) |