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

Primary Purpose

Hemiparesis After Stroke, Traumatic Brain Injury

Status
Unknown status
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Placebo injection
Botulinum toxin injection
Placebo injection and botulinum toxin injection
Sponsored by
Assistance Publique - Hôpitaux de Paris
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hemiparesis After Stroke focused on measuring Muscle spasticity, Botulinum toxin

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Henri Mondor HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Placebo Comparator

Active Comparator

Active Comparator

Arm Label

Group 1

Group 2

Group 3

Arm 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.

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.

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Change ambulation speed at comfortable and maximal speed, barefoot and with shoes over 10 meters
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
Maximal amplitude and speed of passive ankle dorsiflexion at late stance phase, measured in gait kinematic recording, at comfortable and maximal speed
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
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.
Cocontraction indices of rectus femoris and soleus during the first half of swing phase, calculating the ratio MRVSP/MVIE for each of these muscles.
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.
Inappropriate Contraction Indices of soleus during the first half of stance phase, calculating the ratio MRVSP / MVIE
Spasticity Angle et grade of rectus femoris and soleus (Five Step Assessment)
Weakness Angle of rectus femoris and soleus (Five Step Assessment)
Quality of life measured by EQ5D
Mean weekly number of steps
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)
Step length at comfortable and maximal speed, barefoot and with shoes over 10 meters
Step cadence at comfortable and maximal speed, barefoot and with shoes over 10 meters
Physiological Cost Index (PCI) over a walking test of 2 minutes at maximal speed with shoes

Full Information

First Posted
December 23, 2016
Last Updated
April 13, 2017
Sponsor
Assistance Publique - Hôpitaux de Paris
Collaborators
Merz Pharmaceuticals GmbH
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1. Study Identification

Unique Protocol Identification Number
NCT03119948
Brief Title
Partial Blocks of Rectus Femoris and Soleus With Botulinum Toxin Type A (Xeomin®) to Improve Gait in Hemiparesis
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
December 2016
Overall Recruitment Status
Unknown status
Study Start Date
December 2014 (undefined)
Primary Completion Date
November 2017 (Anticipated)
Study Completion Date
December 2018 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris
Collaborators
Merz Pharmaceuticals GmbH

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hemiparesis After Stroke, Traumatic Brain Injury
Keywords
Muscle spasticity, Botulinum toxin

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
66 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Group 1
Arm Type
Placebo Comparator
Arm 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.
Arm Title
Group 2
Arm Type
Active Comparator
Arm 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.
Arm Title
Group 3
Arm Type
Active Comparator
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Placebo injection
Intervention 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. 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
Intervention Type
Drug
Intervention Name(s)
Botulinum toxin injection
Intervention 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. 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.
Intervention Type
Drug
Intervention Name(s)
Placebo injection and botulinum toxin injection
Intervention 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.. 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.
Primary Outcome Measure Information:
Title
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
Time Frame
Preinjection visit (D1) and 3 weeks post injection (D21)
Secondary Outcome Measure Information:
Title
Change ambulation speed at comfortable and maximal speed, barefoot and with shoes over 10 meters
Time Frame
Day 1 and Day 21
Title
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
Time Frame
Day 1 and Day 21
Title
Maximal amplitude and speed of passive ankle dorsiflexion at late stance phase, measured in gait kinematic recording, at comfortable and maximal speed
Time Frame
Day 1 and Day 21
Title
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
Description
calculating the mean rectified voltage over 100 ms around the peak of rectified EMG on each of these muscles
Time Frame
Day 1 and Day 21
Title
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.
Time Frame
Day 1 and Day 21
Title
Cocontraction indices of rectus femoris and soleus during the first half of swing phase, calculating the ratio MRVSP/MVIE for each of these muscles.
Time Frame
Day 1 and Day 21
Title
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.
Time Frame
Day 1 and Day 21
Title
Inappropriate Contraction Indices of soleus during the first half of stance phase, calculating the ratio MRVSP / MVIE
Time Frame
Day 1 and Day 21
Title
Spasticity Angle et grade of rectus femoris and soleus (Five Step Assessment)
Time Frame
Day 1, Day 21, Day 60
Title
Weakness Angle of rectus femoris and soleus (Five Step Assessment)
Time Frame
Day 1, Day 21, Day 60
Title
Quality of life measured by EQ5D
Time Frame
Day 1, Day 60
Title
Mean weekly number of steps
Time Frame
Between Day-15 and Day1, Day7 and Day21 and between Day45 and Day60
Title
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)
Time Frame
Day 1, Day 21, Day 60
Title
Step length at comfortable and maximal speed, barefoot and with shoes over 10 meters
Time Frame
Day 1 and Day 21
Title
Step cadence at comfortable and maximal speed, barefoot and with shoes over 10 meters
Time Frame
Day 1 and Day 21
Title
Physiological Cost Index (PCI) over a walking test of 2 minutes at maximal speed with shoes
Time Frame
Day 1 and Day 21

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jean-Michel GRACIES, MD, PhD
Phone
(0)1.49.81.30.61
Ext
+33
Email
jean-michel.gracies@aphp.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jean-Michel GRACIES, MD, PhD
Organizational Affiliation
Assistance Publique - Hôpitaux de Paris
Official's Role
Study Chair
Facility Information:
Facility Name
Henri Mondor Hospital
City
Creteil
ZIP/Postal Code
94010
Country
France
Individual Site Status
Recruiting

12. IPD Sharing Statement

Citations:
PubMed Identifier
34438333
Citation
Ghedira M, Albertsen IM, Mardale V, Loche CM, Vinti M, Gracies JM, Bayle N, Hutin E. Agonist and antagonist activation at the ankle monitored along the swing phase in hemiparetic gait. Clin Biomech (Bristol, Avon). 2021 Oct;89:105459. doi: 10.1016/j.clinbiomech.2021.105459. Epub 2021 Aug 20.
Results Reference
derived

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

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