Low or High Botox Dilution for the Hemiplegic Gait?

Post Stroke Spastic Hemiplegia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04630873
• Other study ID #: UIoannina 2
• Status: Recruiting
• Phase: Phase 1
• Start date: November 20, 2020
• Est. completion date: December 1, 2024

Study information

• Verified date: March 2023
• Source: University of Ioannina
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: December 1, 2024
• Est. primary completion date: August 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Gait Disorders, Neurologic
• Hemiplegia
• Post Stroke Spastic Hemiplegia

Intervention

Drug:
• Botulinum toxin
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.

Diagnostic Test:
• gait analysis
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:

Locations

Country	Name	City	State
Greece	Department of Physical Medicine and Rehabilitation, University Hospital of Ioannina	Ioannina

Sponsors (1)

Lead Sponsor	Collaborator
University of Ioannina

Country where clinical trial is conducted

Greece, 

References & Publications (5)

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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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