Clinical trial NCT04630873: Low or High Botox Dilution for the Hemiplegic Gait?
Official title: Different Dilutions and Efficacy of Botulin Toxin in the Correction of the Hemiplegic Gait
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Post Stroke Spastic Hemiplegia
Keywords: stroke
hemiplegia
Lead sponsor: University of Ioannina
Sponsor class: OTHER
First posted: 2020-11-16
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Intervention 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.
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change of Ankle motion from baseline to 1 month postinjection
timeFrame: Day 1 (baseline) and at 1 month postinjection
measure: Change of modifies Ashworth scale (from 0 to 4, higher grade means worse spasticity) of the ankle from baseline to 1 month postinjection
timeFrame: Day 1 (baseline) and at 1 month postinjection
measure: Change of standing balance from baseline to 1 month postinjection
timeFrame: Day 1 (baseline) and at 1 month postinjection
measure: Change of walking balance from baseline to 1 month postinjection
timeFrame: Day 1 (baseline) and at 1 month postinjection
Secondary outcomes:
Other outcomes:
Locations:
city: Ioannina
country: Greece
facility: Department of Physical Medicine and Rehabilitation, University Hospital of Ioannina
Study officials:
References:
citation: Francisco GE, Boake C, Vaughn A. Botulinum toxin in upper limb spasticity after acquired brain injury: a randomized trial comparing dilution techniques. Am J Phys Med Rehabil. 2002 May;81(5):355-63. doi: 10.1097/00002060-200205000-00007.
citation: Lee LR, Chuang YC, Yang BJ, Hsu MJ, Liu YH. Botulinum toxin for lower limb spasticity in children with cerebral palsy: a single-blinded trial comparing dilution techniques. Am J Phys Med Rehabil. 2004 Oct;83(10):766-73. doi: 10.1097/01.phm.0000137314.38806.95.
citation: Gracies JM, Lugassy M, Weisz DJ, Vecchio M, Flanagan S, Simpson DM. Botulinum toxin dilution and endplate targeting in spasticity: a double-blind controlled study. Arch Phys Med Rehabil. 2009 Jan;90(1):9-16.e2. doi: 10.1016/j.apmr.2008.04.030.
citation: Shaari CM, Sanders I. Quantifying how location and dose of botulinum toxin injections affect muscle paralysis. Muscle Nerve. 1993 Sep;16(9):964-9. doi: 10.1002/mus.880160913.
citation: Pearce LB, Borodic GE, First ER, MacCallum RD. Measurement of botulinum toxin activity: evaluation of the lethality assay. Toxicol Appl Pharmacol. 1994 Sep;128(1):69-77. doi: 10.1006/taap.1994.1181.