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

NCT03119948 | Unknown Phase 2 DMC

• 2 other identifiers: P1011072013-005088-13
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

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.

Conditions

Hemiparesis After Stroke; Traumatic Brain Injury

Keywords

Muscle spasticity; Botulinum toxin

Outcome Measures

Primary Outcomes (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

  Preinjection visit (D1) and 3 weeks post injection (D21)

Secondary Outcomes (16)

• Change ambulation speed at comfortable and maximal speed, barefoot and with shoes over 10 meters

  Day 1 and Day 21

• 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

• 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

• 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

• 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

Study Arms (3)

Group 1

PLACEBO COMPARATOR

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

Group 2

ACTIVE COMPARATOR

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

Group 3

ACTIVE COMPARATOR

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

Interventions

Placebo injection DRUG

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

Group 1

Botulinum toxin injection DRUG

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.

Group 3

Placebo injection and botulinum toxin injection DRUG

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.

Group 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• Merz Pharmaceuticals GmbH: collaborator

Study Sites (1)

Henri Mondor Hospital

Créteil, 94010, France

RECRUITING

Related Publications (1)

• 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). 2021 Oct;89:105459. doi: 10.1016/j.clinbiomech.2021.105459. Epub 2021 Aug 20.

  PMID: 34438333 DERIVED

MeSH Terms

Conditions

Brain Injuries, Traumatic; Muscle Spasticity

Interventions

Botulinum Toxins

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Muscular Diseases; Musculoskeletal Diseases; Muscle Hypertonia; Neuromuscular Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Metalloproteases; Bacterial Proteins; Proteins; Amino Acids, Peptides, and Proteins; Bacterial Toxins; Toxins, Biological; Biological Factors

Study Officials

• Jean-Michel GRACIES, MD, PhD

  Assistance Publique - Hôpitaux de Paris

  STUDY CHAIR

Central Study Contacts

Jean-Michel GRACIES, MD, PhD

CONTACT

(0)1.49.81.30.61; jean-michel.gracies@aphp.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 23, 2016
• First Posted: April 19, 2017
• Study Start: December 1, 2014
• Primary Completion: November 1, 2017
• Study Completion: December 1, 2018
• Last Updated: April 19, 2017

Record last verified: 2016-12

Locations

FR (1)