Low or High Botox Dilution for the Hemiplegic Gait?

Study Overview
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Brief Summary
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There is debate regarding the efficiency of different dilutions of Botulin toxin type A (BTX-A) injections. Some authors believe that highly diluted BTX-A injections achieve greater neuromuscular blockade resulting in higher spasticity reduction. On the other hand, other researchers suggest that there is no difference in spasticity decrease if either high or low volume toxin is being injected. Studies on this subject lack either the design or the power of study was low. Therefore, there is no clear guideline for an optimal botulinum toxin dilution protocol. In an attempt to have a better understanding, a cross over study was designed. The material will be patients with spastic hemiparesis which will be treated with Botulin toxin at different dilutions. Gait analysis will be used for the evaluation of the Botulin toxin injection on gait improvement. To the best of our knowledge such a trial hasn't been performed yet.

Detailed Description
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There is an ongoing controversy regarding the effect of different dilutions in the efficacy of Botulin toxin type A (BTX-A) injections. Some authors believe that highly diluted BTX-A injections achieve greater neuromuscular blockade resulting in higher spasticity reduction. They are arguing that BTX-A in high dilution is the optimal choice especially when bigger muscles are injected, for the large volume of fluid administered into the muscle will carry the BTX-A molecules to endplates remote from the injection site. Two animal studies suggest that increasing the volume of diluents is a potential strategy in order to achieve a more efficient and cost-effective manner of BTX-A treatment. An attempt to quantify how the location of BTX-A injection affects the drug effect was made, which revealed that injecting only 0.5 cm away from the motor endplates yielded a 50% decrease in paralysis2. A newer double-blinded study by JM Gracies et al performed on humans comes to the same conclusion, that high volume dilution provides greater neuromuscular block and spasticity reduction than a low volume dilution. On the other hand, other researchers suggest that there is no difference in spasticity decrease if either high or low volume toxin is being injected. Previous studies lack either the design or the power of study was low. Therefore, there is no clear guideline for an optimal botulinum toxin dilution protocol.

Official Title
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Different Dilutions and Efficacy of Botulin Toxin in the Correction of the Hemiplegic Gait

Conditions
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Post Stroke Spastic Hemiplegia

Intervention / Treatment
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* Drug: Botulinum toxin
* Diagnostic Test: gait analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: equinovarus deformity with an average 3 on Ashworth spasticity scale able to walk indoors either freely or with a cane. Exclusion Criteria: patients suffering from any mental illness that would disturb the gait pattern patients suffering from musculoskeletal diseases that overtly interfere with the gait

Ages Eligible for Study
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Minimum Age: 18 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: Non-Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: In a sequential manner, every second patient that will meet our inclusion criteria will be treated with a low concentration of the drug during their first visit at our outpatient clinic. Then, after a safe washout period of 6 months, the same patients will be injected with a high concentration of the drug. The same procedure will be inversely performed in the other half of the patients.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: LOW-HIGH VOLUME<br>Initially a low volume of the drug (100IU botulinum toxin diluted in 2 ml) after a safe washout period of 6 months the same patients will be injected with a high volume (100IU botulinum toxin in 4 ml) of the drug. | Drug: Botulinum toxin<br>* The triceps surae along with the posterior tibialis muscle will be injected. The units that will be injected are the average being injected in our University Clinic. I.e. 50 units for each head of the gastrocnemius muscle- single injection site, 100 units for the soleus muscle- two injection sites and 50 units for the posterior tibialis muscle- single injection site.<br>Diagnostic Test: gait analysis<br>* The gait analysis will be performed with two systems. A foot pressure sensitivity walkway (medicapteurs Win-Track), and an IMU network system (RehaGait Pro) using seven IMU's placed in specific anatomical positions. In combination those two systems can provide a wide range of spatiotemporal analytics of gait:<br>* Other names: RehaGait Pro;|
| Experimental: HIGH-LOW VOLUME<br>initially a high volume of the drug (100IU botulinum toxin diluted in 4 ml) after a safe washout period of 6 months the same patients will be injected with a low volume (100IU botulinum toxin in 2 ml) of the drug. | Drug: Botulinum toxin<br>* The triceps surae along with the posterior tibialis muscle will be injected. The units that will be injected are the average being injected in our University Clinic. I.e. 50 units for each head of the gastrocnemius muscle- single injection site, 100 units for the soleus muscle- two injection sites and 50 units for the posterior tibialis muscle- single injection site.<br>Diagnostic Test: gait analysis<br>* The gait analysis will be performed with two systems. A foot pressure sensitivity walkway (medicapteurs Win-Track), and an IMU network system (RehaGait Pro) using seven IMU's placed in specific anatomical positions. In combination those two systems can provide a wide range of spatiotemporal analytics of gait:<br>* Other names: RehaGait Pro;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of Ankle motion from baseline to 1 month postinjection | range of motion of ankle during gait | Day 1 (baseline) and at 1 month postinjection | 
| Change of modifies Ashworth scale (from 0 to 4, higher grade means worse spasticity) of the ankle from baseline to 1 month postinjection | spasticity measurement | Day 1 (baseline) and at 1 month postinjection | 
| Change of standing balance from baseline to 1 month postinjection | measuring the ground force position when standing | Day 1 (baseline) and at 1 month postinjection | 
| Change of walking balance from baseline to 1 month postinjection | measuring the ground force position when walking | Day 1 (baseline) and at 1 month postinjection | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stroke, hemiplegia