Low or High Botox Dilution for the Hemiplegic Gait?

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

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.

Study Overview

• Status: Recruiting
• Conditions: Post Stroke Spastic Hemiplegia
• Intervention / Treatment: Drug: Botulinum toxin; Diagnostic test: gait analysis

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 Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• Greece
  • Ioannina, Greece, 45100
    • Recruiting
    • Department of Physical Medicine and Rehabilitation, University Hospital of Ioannina
    • Contact: Avraam Ploumis; Phone Number: 6932080701; Email: aploumis@uoi.gr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: LOW-HIGH VOLUME; 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; 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: Other Names: medicapteurs Win-Track; RehaGait Pro
Experimental: HIGH-LOW VOLUME; 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; 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: Other Names: medicapteurs Win-Track; RehaGait Pro

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Ioannina

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): November 20, 2020
• Primary Completion (Estimated): August 1, 2025
• Study Completion (Estimated): August 1, 2025

Study Registration Dates

• First Submitted: October 31, 2020
• First Submitted That Met QC Criteria: November 10, 2020
• First Posted (Actual): November 16, 2020

Study Record Updates

• Last Update Posted (Actual): December 6, 2024
• Last Update Submitted That Met QC Criteria: December 4, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: stroke; hemiplegia
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Paralysis; Gait Disorders, Neurologic; Hemiplegia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Membrane Transport Modulators; Cholinergic Agents; Acetylcholine Release Inhibitors; Botulinum Toxins
• Other Study ID Numbers: UIoannina 2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes