Low or High Botox Dilution for the Hemiplegic Gait?

Phase 1

Recruiting

• Conditions: Post Stroke Spastic Hemiplegia
• Interventions: Drug: Botulinum toxin; Diagnostic Test: gait analysis

• Registration Number: NCT04630873
• Lead Sponsor: University of Ioannina

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.

Study Timeline

• Study First Submitted: 2020-10-31
• Study First Submitted QC: 2020-11-10
• Study First Posted: 2020-11-16
• Study Start: 2020-11-20
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-04
• Last Update Posted: 2024-12-06
• Primary Completion: 2025-08-01
• Study Completion: 2025-08-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 20

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
LOW-HIGH VOLUME	gait analysis	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.
HIGH-LOW VOLUME	gait analysis	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.
LOW-HIGH VOLUME	Botulinum toxin	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.
HIGH-LOW VOLUME	Botulinum toxin	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.

Primary Outcome Measures

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

Trial Locations

Locations (1)

Department of Physical Medicine and Rehabilitation, University Hospital of Ioannina; 🇬🇷 Ioannina, Greece