Botulinum Toxin A Adult Gastrocnemius Muscle Study

Study Overview
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Brief Summary
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The study aims to compare the effectiveness of BOTOX-A® (botulinun toxin A) placed between two different injection sites, namely at the proximal portion of the gastrocnemius(GCM) versus at the midbelly of the GCM.

Detailed Description
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Previous studies have used the midbelly of a muscle as the position where the motor endplates are most densely located. The reasoning behind this method was based on the previous works that showed most bands of cholinesterase activity to be located in specific topographical patterns at the center of the muscle fiber. These results have been used as landmarks to place the injections. Current standard guidelines recommend that botulinum toxin be placed at the 4 quadrants of the midbelly portion of the gastrocnemius (GCM) muscle. However, recent cadaveric research studies on the distribution of the intramuscular endings of the GCM suggest that the highest branch density is found within the upper 20-30% length of the calf. Therefore, in accordance to the theory that effect of botulinum toxin are greatest at sites where the intramuscular endings are most dense, the location where these toxins should be placed would be at these proximal sites of the GCM rather than at the midbelly. 40 recruited patients will be allocated into either the intramuscular ending targeted (ie.upper portion of calf) or midbelly targeted group. Each subject will undergo a total number of 4 assessments; prior to the injection and 2,4and 8 weeks post injection.

Official Title
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An Efficacy Comparison of Botulinum Toxin A Injection Into Two Different Sites in Gastrocnemius Muscle for the Treatment of Spastic Patients, Randomized Controlled Trial

Conditions
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Muscle Spasticity, Stroke

Intervention / Treatment
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* Drug: BOTOX-A®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, 20 < age < 70 year old Hemiplegia documented after ischemic or hemorrhagic stroke, documented by CT (computed tomography) or MRI (magnetic resonance imaging) scan Time between the onset of stroke < 24 months Individuals who have been medically stable for at least 4 weeks prior to study enrollment Confirmed equinovarus with spastic hypertonia of the ankle Spasticity as defined by a MAS greater than grade 1 + Botulinum toxin -naive patients Participants who can complete the 10 meter walking test with caregiver or walking tool assistance within 8 and 45 seconds, on 2 occasions Participants who will have stable treatment regimen and concomitant medication during the trial period Exclusion Criteria: The patient has any of the following medical conditions that is contraindication to botulinum toxin exposure; pregnancy, lactation, neuromuscular disease, aminoglycoside, antibiotic concurrent to botulinum toxin treatment Fixed contracture of the ankle, previous history of surgical procedure performed on the ankle Cognitive deficit that disables patients to give informed consent to the procedure Concomitant progression of any CNS (central nervous system) or PNS (peripheral nervous system), or myopathy, or uncontrolled seizure. Underlying CNS insult should be controlled and in stable condition with no further risk of progression and further deterioration of patient's current neurological status. Those with multiple sclerosis or multiple systemic atrophy are to be excluded Significant cutaneous or joint inflammation URI or other systemic infection that would mandate the use of antibiotic concurrent to botulinum toxin injection Anticoagulation treatment with INR (International Normalized Ratio) greater than 3.0 Upper extremity spasticity greater than MAS grade 4 that may limit gait function Subjects with previous episodes of motor point block injection using phenol or other chemodenervating agents Subjects with intrathecal baclofen pump

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 70 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intramuscular ending Targeting<br>Botox 200 units placed at the upper 2/10-3/10 length of the GCM | Drug: BOTOX-A®<br>* 200 units, single treatment only<br>* Other names: Generic Name: Botulinum toxin type A;|
| Active Comparator: Midbelly Targeting<br>A total of 200 units will be placed at the four quadrants of the midbelly portion of the GCM. | Drug: BOTOX-A®<br>* 200 units, single treatment only<br>* Other names: Generic Name: Botulinum toxin type A;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline for EMG (electromyogram) activity | Surface EMG | week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline of GCM tone a measured on the Modified Ashworth Scale (MAS) |  | Change from baseline at 8 weeks | 
| Change from baseline of Ankle Range of motion | Passive range of motion of the ankle at resting state with the use of goniometer | Change from baseline at 8 weeks | 
| Change from baseline of gait speed with 10 meters walk test | Change from baseline at 8 weeks | Change from baseline at 8 weeks | 
| Change from baseline of ABILOCO scale |  | Change from baseline at 8 weeks | 
| Change from baseline of Disability Assessment Scale |  | Change from baseline at 8 weeks | 
| Change from baseline of Functional Ambulation Category Scale |  | Change from baseline at 8 weeks | 
| Change of baseline of Lindmark Modified Fugyl Meyer Scale |  | Change from baseline at 8 weeks | 
| Change from baseline of Tardieu angle of ankle |  | Change from baseline at 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Muscle spasticity, Stroke, Botulinum Toxins, Lower extremity, Ankle