Effect of Repeated Injections of Higher Doses of Botulinum Toxin on Lower Limb of Spastic Hemiplegic Patients on Gait.

Not Applicable

Completed

• Conditions: Stroke
• Interventions: Drug: Xeomin Injectable Product

• Registration Number: NCT04544280
• Lead Sponsor: Cliniques universitaires Saint-Luc- Université Catholique de Louvain

Brief Summary

1. To show that repeated injections of higher doses of botulinum toxin are significantly more effective than the injection of unique, lower doses, on gait function.

2. To describe the effect of repeated injections of botulinum toxin on the muscle structure in terms of volume, fat accumulation and fibrosis, by means of MRI studies

Detailed Description

1. A prospective, interventional, multi-centre, open-labeled study will be carried out. Sixty stroke patients will be recruited (from the Rehabilitation Ward of Cliniques Universitaires Saint-Luc (UCLouvain), or Centre Hospitalier Universitaire de Mont Godinne (UCLouvain), or in the out-patients clinic), if they have an indication for focal chemical denervation (by botulinum toxin injections) to treat lower limb hyper-resistance (spasticity).

Inclusion criteria: adults (\>18 years old), hemiparesis secondary to stroke, date of stroke\>3 months ago, lower limb hyper-resistance responsible of gait impairment, focal chemical denervation indication, ability to walk on a treadmill.

Exclusion criteria: aphasia or major cognitive impairments limiting the functional evaluation, neurological or orthopedic affections interfering with the studied lower limb's function, BONT injections on the lower limb during the last 3 months, contraindication to BONT injections (underlying neuromuscular disease) and no contraindication to undergo an MRI study.

Patients will benefit from 3 sessions of botulinum toxin (Xeomeen) injections at 3 months intervals. During the first session, 400 U of Xeomeen will be injected in the lower limb of the patient (and upper limb, if needed). During the second session, 600U of Xeomeen will be injected and during the third session, 800Units of Xeomeen will be injected (in the lower limb of the patient-and upper limb, if needed-). The injections will be based on the clinical evaluation carried out by one of the investigators, who are medical doctors, specialized in Physical and Rehabilitation Medicine and have experience with hyper-resistance treatment with botulinum toxin.

Patients will be evaluated just before, a month later and 3 months after each injection session. Functional evaluations are based on the ICF model. Impairment will be evaluated by the clinical examination (range of motion -ROM- with a hand goniometer, MAS and Tardieu scale for spasticity, Fugl-Meyer test for motor control)20; by functional evaluations (10 meters walk test, 6 minutes walk test, timed up and down the stairs test, Timed Up and Go Test) and by a 3D-Quantified Gait Analysis. The limitations in activities of daily life will be evaluated by means of the ABILOCO questionnaire. Quality of life (QoL) will be evaluated with the French version of the Short-Form Health Survey SF-3624.

2. To describe the effect of repeated injections of botulinum toxin (Xeomeen) on the muscle structure in terms of volume, fat accumulation and fibrosis, a lower limb MRI will be performed before, 1-3 days and 1 month after the 1st Xeomeen injection, and 1 month after the 3rd BONT injection, for 4 MRI studies per patient. Twenty hemiplegic subjects will be recruited. They will participate to the complete study protocol, as described for our first objective. Inclusion and exclusion criteria will be the same as previously described.

Statistical analysis: The effects of treatment on continuous variables will be assessed by a one-way (time) repeated-measures analysis of variance (Anova). Ordinal data will be assessed by a non-parametric analysis. A Chi2 test will be used to compare the distributions of qualitative variables. Testing will be performed with a p-value \<0,05.

Study Timeline

• Study Start: 2018-09-13
• Study First Submitted: 2020-09-03
• Study First Submitted QC: 2020-09-03
• Study First Posted: 2020-09-10
• Primary Completion: 2021-12-31
• Study Completion: 2021-12-31
• Status Verified: 2023-08
• Last Update Submitted: 2023-08-14
• Last Update Posted: 2023-08-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 32

Inclusion Criteria

• hemiparesis secondary to stroke, date of stroke>3 months ago, lower limb hyper resistance responsible of gait impairment, focal chemical denervation indication, ability to walk on a treadmill

Exclusion Criteria

• aphasia or major cognitive impairments limiting the functional evaluation, neurological or orthopedic affections interfering with the studied lower limb's function, botulinum toxin injections on the lower limb during the last 3 months, contraindication to botulinum toxin injections (underlying neuromuscular disease) and no contraindication to undergo an MRI study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Intervention	Xeomin Injectable Product	-

Primary Outcome Measures

Name	Time	Method
Temporo-spatial parameters of gait	7-9 months	Improvement of temporo-spatial parameters of gait as assessed by quantified gait analysis

Secondary Outcome Measures

Name	Time	Method
Muscle structure	7-9 months	Modification of muscle structure (volume, presence of fatty and fibrotic tissue) after repeated botulinum toxin injections as evaluated by MRI imaging.
Segmental kinematics of gait	7-9 months	Improvement of segmental kinematics of gait as assessed by quantified gait analysis
Energetic parameters	7-9 months	Improvement of energetic parameters of gait as assessed by quantified gait analysis

Trial Locations

Locations (2)

Cliniques Universitaire Saint Luc; 🇧🇪 Bruxelles, Belgium

Cliniques Universitaires UCL Mont-Godinne; 🇧🇪 Yvoir, Belgium