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

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ClinicalTrials.gov Identifier: NCT03119948
Recruitment Status : Recruiting
First Posted : April 19, 2017
Last Update Posted : April 19, 2017
Sponsor:
Collaborator:
Merz Pharmaceuticals GmbH
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

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.


Condition or disease Intervention/treatment Phase
Hemiparesis After Stroke Traumatic Brain Injury Drug: Placebo injection Drug: Botulinum toxin injection Drug: Placebo injection and botulinum toxin injection Phase 2

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 66 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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 Start Date : December 2014
Estimated Primary Completion Date : November 2017
Estimated Study Completion Date : December 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Botox

Arm Intervention/treatment
Placebo Comparator: Group 1
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.
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


Active Comparator: Group 2
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.
Drug: 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.


Active Comparator: Group 3
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.
Drug: 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.





Primary Outcome Measures :
  1. 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 Measures :
  1. Change ambulation speed at comfortable and maximal speed, barefoot and with shoes over 10 meters [ Time Frame: Day 1 and Day 21 ]
  2. 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 ]
  3. 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 ]
  4. 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 [ Time Frame: Day 1 and Day 21 ]
    calculating the mean rectified voltage over 100 ms around the peak of rectified EMG on each of these muscles

  5. 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 ]
  6. 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 ]
  7. 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 ]
  8. Inappropriate Contraction Indices of soleus during the first half of stance phase, calculating the ratio MRVSP / MVIE [ Time Frame: Day 1 and Day 21 ]
  9. Spasticity Angle et grade of rectus femoris and soleus (Five Step Assessment) [ Time Frame: Day 1, Day 21, Day 60 ]
  10. Weakness Angle of rectus femoris and soleus (Five Step Assessment) [ Time Frame: Day 1, Day 21, Day 60 ]
  11. Quality of life measured by EQ5D [ Time Frame: Day 1, Day 60 ]
  12. Mean weekly number of steps [ Time Frame: Between Day-15 and Day1, Day7 and Day21 and between Day45 and Day60 ]
  13. 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 ]
  14. Step length at comfortable and maximal speed, barefoot and with shoes over 10 meters [ Time Frame: Day 1 and Day 21 ]
  15. Step cadence at comfortable and maximal speed, barefoot and with shoes over 10 meters [ Time Frame: Day 1 and Day 21 ]
  16. Physiological Cost Index (PCI) over a walking test of 2 minutes at maximal speed with shoes [ Time Frame: Day 1 and Day 21 ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03119948


Contacts
Contact: Jean-Michel GRACIES, MD, PhD (0)1.49.81.30.61 ext +33 jean-michel.gracies@aphp.fr

Locations
France
Henri Mondor Hospital Recruiting
Creteil, France, 94010
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Merz Pharmaceuticals GmbH
Investigators
Study Chair: Jean-Michel GRACIES, MD, PhD Assistance Publique - Hôpitaux de Paris

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT03119948     History of Changes
Other Study ID Numbers: P101107
2013-005088-13 ( EudraCT Number )
First Posted: April 19, 2017    Key Record Dates
Last Update Posted: April 19, 2017
Last Verified: December 2016

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Muscle spasticity
Botulinum toxin

Additional relevant MeSH terms:
Brain Injuries
Brain Injuries, Traumatic
Paresis
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System
Wounds and Injuries
Neurologic Manifestations
Signs and Symptoms
Botulinum Toxins
Botulinum Toxins, Type A
onabotulinumtoxinA
abobotulinumtoxinA
Acetylcholine Release Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Cholinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Neuromuscular Agents
Peripheral Nervous System Agents