Partial Blocks of Rectus Femoris and Soleus With Botulinum Toxin Type A (Xeomin®) to Improve Gait in Hemiparesis "GENUFLEX"

Recruiting

Phase 2 Results N/A

Trial Description

The most common motor deficiency after stroke or traumatic brain injury is hemiparesis. Most hemiparetic patients recover walking, but rarely with a speed permitting easy ambulation outdoors with family or friends. One of the mechanisms of gait impairment in hemiparesis is insufficient active hip flexion during swing phase, which leads to insufficient ground clearing at swing phase, with associated gait slowness and risks of fall.
The main hypothesis behind the present study is that insufficient hip flexion during hemiparetic gait is partly due to overactivity of rectus femoris. Focal treatment of lower limb muscle overactivity using botulinum toxin has not been demonstrated to increase walking speed in hemiparesis as yet. However, most studies have focused distally, on improving foot dorsiflexion only. The purpose of this study is to compare the effects of botulinum toxin injection and placebo in rectus femoris (RF) + plantar flexors versus plantar flexors only.

Detailed Description

Randomized, double blind, parallel-group study in chronic, non-evolutive brain damaged patients (>6 months since stroke or brain trauma) and ambulating at <1.3 m/sec at maximal speed barefoot (AT10) Group 1: 150U (x 7.5 ml) placebo Sol + 150U (x 7.5 ml) placebo RF + 100U (5ml) placebo distributed between tibialis posterior, FHL (flexor hallucis longus), FCB (flexor digitorum brevis), gastrocnemius muscles or peroneus longus, based upon investigator clinical judgment.
Group 2: 150U (x 7.5 ml) Xeomin® 20U/ml Sol + 150U (x 7.5 ml) placebo RF + 100U (5ml) Xeomin® distributed between tibialis posterior, FHL (flexor hallucis longus), FCB (flexor digitorum brevis), gastrocnemius muscles or peroneus longus, based upon investigator clinical judgment.
Group 3: 150U (x 7.5 ml) Xeomin® 20U/ml Sol + 150U (x 7.5 ml) Xeomin® 20U/ml RF + 100U (5ml) Xeomin® distributed between tibialis posterior, FHL (flexor hallucis longus), FCB (flexor digitorum brevis), gastrocnemius muscles or peroneus longus, based upon investigator clinical judgment.

Conditions

Interventions

  • Botulinum toxin injection Drug
    Intervention Desc: Botulinum toxin type A in soleus and in rectus femoris, and Botulinum toxin type A in additional muscles as per investigator's choice among tibialis posterior, toe flexors (long or short), gastrocnemius muscles or peroneus longus. 150U (x 7.5 ml) Xeomin® 20U/ml Sol + 150U (x 7.5 ml) Xeomin® 20U/ml RF + 100U (5ml) Xeomin® distributed between tibialis posterior, FHL (flexor hallucis longus), FCB (flexor digitorum brevis), gastrocnemius muscles or peroneus longus, based upon investigator clinical judgment.
    ARM 1: Kind: Experimental
    Label: Group 3
    Description: Botulinum toxin type A in soleus and in rectus femoris, and Botulinum toxin type A in additional muscles as per investigator's choice among tibialis posterior, toe flexors (long or short), gastrocnemius muscles or peroneus longus.
  • Placebo Injection Drug
    Other Names: Placebo
    Intervention Desc: Placebo in soleus and placebo in rectus femoris, and placebo in additional muscles as per investigator's choice among tibialis posterior, toe flexors (long or short), gastrocnemius muscles or peroneus longus. 150U (x 7.5 ml) placebo Sol + 150U (x 7.5 ml) placebo RF + 100U (5ml) placebo distributed between tibialis posterior, FHL (flexor hallucis longus), FCB (flexor digitorum brevis), gastrocnemius muscles or peroneus longus, based upon investigator clinical judgment
    ARM 1: Kind: Experimental
    Label: Group 1
    Description: Placebo in soleus and placebo in rectus femoris, and placebo in additional muscles as per investigator's choice among tibialis posterior, toe flexors (long or short), gastrocnemius muscles or peroneus longus.
  • Placebo injection and botulinum toxin injection Drug
    Intervention Desc: Botulinum toxin type A in soleus and placebo in rectus femoris, and Botulinum toxin type A in additional muscles as per investigator's choice among tibialis posterior, toe flexors (long or short), gastrocnemius muscles or peroneus longus.. 150U (x 7.5 ml) Xeomin® 20U/ml Sol + 150U (x 7.5 ml) placebo RF + 100U (5ml) Xeomin® distributed between tibialis posterior, FHL (flexor hallucis longus), FCB (flexor digitorum brevis), gastrocnemius muscles or peroneus longus, based upon investigator clinical judgment.
    ARM 1: Kind: Experimental
    Label: Group 2
    Description: Botulinum toxin type A in soleus and placebo in rectus femoris, and Botulinum toxin type A in additional muscles as per investigator's choice among tibialis posterior, toe flexors (long or short), gastrocnemius muscles or peroneus longus.

Outcomes

Type Measure Time Frame Safety Issue
Primary Change in maximum speed of barefoot ambulation without technical assistance over 10 meters, between the pre-injection visit (D1) and 3 weeks (D21) post injection Preinjection visit (D1) and 3 weeks post injection (D21)
Secondary Change ambulation speed at comfortable and maximal speed, barefoot and with shoes over 10 meters Day 1 and Day 21
Secondary Maximal amplitude and speed of active hip flexion and passive knee flexion during swing phase, measured in gait kinematic recording, at comfortable and maximal speed Day 1 and Day 21
Secondary Maximal amplitude and speed of passive ankle dorsiflexion at late stance phase, measured in gait kinematic recording, at comfortable and maximal speed Day 1 and Day 21
Secondary Maximal voluntary isometric EMG (MVIE) of rectus femoris and soleus, measured by surface EMG, in an isometric position with hip at 15° flexion, knee at 30° flexion, and ankle at 80° of dorsiflexion Day 1 and Day 21
Secondary Mean rectified voltage of rectus femoris and soleus during the first half of swing phase (MRVSP), from toe-off to maximal hip flexion, measured by surface EMG (electrodes 2 cm apart) immediately after MVIE measure. Day 1 and Day 21
Secondary Cocontraction indices of rectus femoris and soleus during the first half of swing phase, calculating the ratio MRVSP/MVIE for each of these muscles. Day 1 and Day 21
Secondary Mean rectified voltage of soleus during the first half of stance phase (MRVSP), from heel-on to maximal knee extension, measured by surface EMG (electrodes 2 cm apart) immediately after MVIE measure. Day 1 and Day 21
Secondary Inappropriate Contraction Indices of soleus during the first half of stance phase, calculating the ratio MRVSP / MVIE Day 1 and Day 21
Secondary Spasticity Angle et grade of rectus femoris and soleus (Five Step Assessment) Day 1, Day 21, Day 60
Secondary Weakness Angle of rectus femoris and soleus (Five Step Assessment) Day 1, Day 21, Day 60
Secondary Quality of life measured by EQ5D Day 1, Day 60
Secondary Mean weekly number of steps Between Day-15 and Day1, Day7 and Day21 and between Day45 and Day60
Secondary Potential AEs of injections (pain or discomfort during the injection or post injection, or ecchymoses at insertion site) and potential AEs related to the injected drug (muscle weakening, allergies) Day 1, Day 21, Day 60
Secondary Step length at comfortable and maximal speed, barefoot and with shoes over 10 meters Day 1 and Day 21
Secondary Step cadence at comfortable and maximal speed, barefoot and with shoes over 10 meters Day 1 and Day 21
Secondary Physiological Cost Index (PCI) over a walking test of 2 minutes at maximal speed with shoes Day 1 and Day 21

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