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

Traumatic Brain Injury Clinical Trial

— GENUFLEX  

Official title:

Partial Blocks of Rectus Femoris and Soleus With Botulinum Toxin Type A to Improve Gait in Hemiparesis. A Randomized Multicenter Placebo-controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03119948
• Other study ID #: P101107
• Secondary ID: 2013-005088-13
• Status: Recruiting
• Phase: Phase 2
• First received: December 23, 2016
• Last updated: April 13, 2017
• Start date: December 2014
• Est. completion date: December 2018

Study information

• Verified date: December 2016
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Jean-Michel GRACIES, MD, PhD
• Phone: (0)1.49.81.30.61
• Email: jean-michel.gracies[@]aphp.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 66
• Est. completion date: December 2018
• Est. primary completion date: November 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria

• Hemiparesis from stroke, brain trauma, or non evolutive brain tumor >6 months before enrolment

• Hip flexion at swing phase on the paretic side clinically insufficient (rated <15° by the clinical investigator)

• Passive ankle dorsiflexion clinically insufficient at late stance (rated <90° by the clinical investigator)

• Maximal ambulation speed barefoot over 10 metres < 1,3 m/sec

• Age = 18

• Signed consent form

Exclusion Criteria

• Ambulation impossible barefoot

• Passive hip flexion amplitude (with the knee flexed) < 45° on paretic side

• Severe intercurrent disease ou cognitive dysfunction making effective communication or study participation impossible.

• Current anticoagulation with INR> 3,5 ; less than 15 days prior to D1

• Pregnancy, lactation, or premenopause woman not taking contraception

• Hypersensitivity to botulinum toxin or its excipients, myasthenia gravis, Lambert-Eaton syndrome, concomitant aminoside treatment.

• Infection or inflammation at injection sites.

• Injection in lower limb less than 3 months prior to D1

• Person not covered by social security

Related Conditions & MeSH terms

• Brain Injuries
• Hemiparesis After Stroke
• Paresis
• Traumatic Brain Injury

Intervention

Drug:
• Placebo injection
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
• Botulinum toxin injection
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.
• Placebo injection and botulinum toxin injection
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.

Locations

Country	Name	City	State
France	Henri Mondor Hospital	Creteil

Sponsors (2)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris	Merz Pharmaceuticals GmbH

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	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	calculating the mean rectified voltage over 100 ms around the peak of rectified EMG on each of these muscles	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