Study of the Effect of Botulinum Toxin Injection in Rectus Femoris and Triceps on the Length and the Strength During Locomotion in Chronic Hemiparetic Patients (FOLOTOX)

Double Blind Randomized Controlled Study of the Effect of Botulinum Toxin Injection in Rectus Femoris and Triceps on the Length and the Strength of These Muscles During Locomotion in Chronic Hemiparetic Patients

The aim of this randomized controlled study is to quantify the modification during locomotion of chronic hemiparetic patients of the strength and the length of Rectus Femoris and Triceps Surae induced by botulinum toxin injection type A.

The main hypotheses of this study based on previous studies are that botulinum toxin injection increases on one hand the length of the muscle injected during gait and on the other hand decreased the strength of the muscles injected.

The investigators also hypothesized that botulinum toxin injection improved the strength of the antagonist muscles and normalized the pattern of strength of the muscles injected during gait.

Study Overview

• Status: Completed
• Conditions: COMPARISON BETWEEN GROUP TREATED WITH BOTULINUM TOXIN AND PLACEBO
• Intervention / Treatment: Drug: botulinum toxin type A; Drug: injection of NaCl 0.9%

Detailed Description

The aim of this study is to compare versus placebo the effects of BTX-A injection on :

• the maximal length of the muscles injected during gait
• the maximal lengthening velocity of the muscles injected during gait
• the maximal strength of muscles injected during gait
• the inter-limb coordination assessed by continuous relative phase
• the kinematic parameters such as peak knee flexion during swing phase of the gait cycle and peak ankle dorsiflexion during stance phase.

To that end each patient included in the study will be assessed before injection, one month after the BTX-A injection and 3 months after BTX-A injections.

All patients will underwent a clinical examination, a 3D gait analysis and a isokinetic dynamometer analysis.

The comparison of the results in the group treated by BTX-A will permit to show that one month after BTX-A injection peak length during gait of muscles injected, maximal lengthening velocity peak knee flexion during swing phase and peak ankle dorsiflexion increase significantly.

It will also permit to show that the maximal strength of muscles injected decreases whereas the strength of antagonist increases It will also permit to demonstrate that multisite BTX-A injection improve coordination of paretic and non paretic lower limb the inter-group comparison will permit to demonstrate that these modification are mainly due to multisite BTX-A injections.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Bretagne
    • Brest, Bretagne, France, 29290
      • Service de médecine physique et réadaptation CHU de Brest
  • Hauts-de-Seine
    • Garches, Hauts-de-Seine, France, 92380
      • Nicolas Roche
  • Loiret
    • Amilly, Loiret, France, 45420
      • Centre de rééducation de l'ADAPT Montargis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• men or women aged > 18 ans
• unilateral stroke more than 6 months
• ability to walk 10 meters without assistive device
• decrease of peak knee flexion in swing phase of the gait cycle due to a spasticity of Rectus femoris muscle
• plantarflexion in swing phase of the gait cycle due to a spasticity of the triceps surae
• informed consent approved
• oral contraception

Exclusion Criteria:

• Aphasia
• anteriority of lower limb surgery less than 6 months
• underlying disease
• pre-existing neuro-muscular disorders
• pregnancy
• absence of oral contraception
• last botulinum toxin injection < 3months
• hypersensitivity reactions
• co-administration of aminoglycosides

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Botox Injection; Patients treated by botulinum toxin.	Drug: botulinum toxin type A; Experimental arm group: 150 Units in rectus femoris ( 3 ml and 3 points); 70 units in medial gastrocnemius (1.4 ml and 1 point); 70 units in lateral gastrocnemius ( 1.4 ml and 1 point); 60 units in soleus ( 1.2 ml and 3 points); Other Names: Botox® allergan Inc
Placebo Comparator: Saline Solution; Patients treated with saline solution.	Drug: injection of NaCl 0.9%; Placebo comparator group: injection of NaCl 0.9%: 3 ml of NaCl 0.9% in rectus femoris in 3 points; 1.4 ml of NaCl 0.9% in medial gastrocnemius in 1 point; 1.4 ml of Nacl 0.9% in lateral gastrocnemius in 1 point; 1.2 ml of NaCl 0.9% in soleus in 3 points

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measure of the maximal length of the muscles treated by Botulinum	The maximal length of the muscles treated by Botulinum Toxin during locomotion quantified using 3D motion analysis and musculo-skeletal model. This measure will be performed one month after Botulinum toxin injection.	1.5 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The maximal strength measure	The maximal strength developed by injected muscles during gait.	1.5 hours
Inter-segmental coordination measure	The modification of inter-segmental coordination during locomotion induced by botulinum toxin and quantified by continuous relative phase injection	1.5 hours
Measure of joint torque at knee and ankle level.	The modification of joint torque at knee and ankle level induced by botulinum toxin injection.	1.5 hours

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Allergan
• Investigators: Principal Investigator: Nicolas Roche, MD, Physical medicine and rehabilation Department, Hôpital RAYMOND POINCARE, 92380 Garches, France

Publications and helpful links

General Publications

• Supiot A, Geiger M, Bensmail D, Aegerter P, Pradon D, Roche N. Effect of botulinum toxin injection on length and force of the rectus femoris and triceps surae muscles during locomotion in patients with chronic hemiparesis (FOLOTOX). BMC Neurol. 2018 Aug 2;18(1):104. doi: 10.1186/s12883-018-1110-8.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2013
• Primary Completion (Actual): September 5, 2017
• Study Completion (Actual): May 23, 2019

Study Registration Dates

• First Submitted: March 27, 2013
• First Submitted That Met QC Criteria: March 27, 2013
• First Posted (Estimate): April 1, 2013

Study Record Updates

• Last Update Posted (Actual): May 30, 2019
• Last Update Submitted That Met QC Criteria: May 29, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: botulinum toxin injection,3D motion analysis, muscular lengthening,muscle strength
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Cholinergic Agents; Membrane Transport Modulators; Acetylcholine Release Inhibitors; Neuromuscular Agents; Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA
• Other Study ID Numbers: P110136 / AOM11223; 2012-001203-21 (EudraCT Number)