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Upper-limb Active Function and Botulinum Toxin A (ULAFBoT-Stroke)

Primary Purpose

Stroke, Muscle Spasticity, Upper Extremity Paralysis

Status
Recruiting
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Clinical evaluation
Clinical evaluation and Instrumental evaluation
Sponsored by
University Hospital, Toulouse
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Stroke focused on measuring Botulinum toxin, Cerebrovascular Accident, upper-limb movement, spastic cocontraction, electromyography, electroencephalography

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Stroke group :

Inclusion Criteria:

  • Cortical and/or subcortical ischemic or haemorrhagic stroke for at least 6 months;
  • Indication to an injection of BTA in the elbow flexor muscles according to the usual clinical criteria: request of elbow extension improvement with a functional or aesthetic objective;
  • Being under prescription of abobotulinum toxin A (DYSPORT®, Ipsen-Pharma);
  • Ability of active elbow extension> 20 degrees;
  • Limitation of active movement of elbow extension > 15 degrees or decreased or 50% decrease in the active elbow extension rate;
  • Patients who have never been treated with BTX or only a first injection that having targeted the elbow flexors more than 4 months ago;
  • Age> 18 years;
  • Signature of informed consent;
  • Subject affiliated to the social security coverture.

Exclusion Criteria:

  • Passive limitation of elbow extension > 30 degrees;
  • Pain during active movements of elbow flexion/extension;
  • Cognitive disorder with limited comprehension of three basic instructions (like the test of the 3 papers of the MMS);
  • Evolutionary or decompensated neurological disease;
  • Unstabilized epilepsy;
  • Anticoagulant treatment with a curative dose or hemostasis disorder that contraindicates intramuscular injections;
  • Claustrophobia or metallic foreign bodies contraindicated for MRI;
  • General contraindication for botulinum toxin injection: hypersensitivity to the active substance or to one of the excipients, swallowing disorder, chronic respiratory disorders, antecedent of myasthenia or Lambert Eaton syndrome; antecedent of neuromuscular disease; surgery with curarization for less than a month; current treatment with aminoglycoside, aminoquinoline, cyclosporine or anticholinesterase.
  • Presence of skin infection or inflammation at the injection site.
  • Legal incapacity.
  • Pregnant or breastfeeding woman;
  • Woman with a desire to become pregnant within 18 months.
  • Non-menopausal woman (a postmenopausal state is defined as no menses for 12 months without an alternative medical cause) who does not use one of the following contraceptive methods considered highly effective : intrauterine device, oestroprogestonic contraception or progestogen hormonal contraception associated with inhibition of ovulation, intrauterine hormone-releasing system, or bilateral tubal occlusion.

Control group

  • inclusion criteria:

    • Age> 18 years
    • Signature of informed consent.

  • exclusion criteria:

    • History of orthopedic or neurologic disorders;
    • Subject expert in a sport intensively requiring the upper limbs (at least departmental competition level);
    • Legal incapacity.

Sites / Locations

  • University Hospital ToulouseRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Stroke patients

Control Group

Arm Description

40 stroke patients : Injection of the TBA and the investigator will compare the measure of spastic cocontraction index (ICCS) during different movement before versus 4 weeks after injection of TBA : Clinical evaluation and Instrumental evaluation TBA injections are performed as part of routine care

The control group : Clinical evaluation consists in the search for criteria of non-inclusion and manual laterality score The will ha an Instrumental review just like the patient : concomitant evaluation of the 3D kinematics of the dominant upper limb, EMG of the triceps brachii muscles, biceps brachii, brachio-radial, brachial; associated with EEG recording, during active extension and elbow flexion movements, of the dominant upper extremity, at spontaneous and maximal speed Clinical evaluation

Outcomes

Primary Outcome Measures

Measurement of the spastic co-contraction index from the EMG signal
Measurement of the spastic co-contraction index (SCCI) during a maximal active elbow extension, obtained from the EMG signal of the elbow muscles on the paretic side before / after BTX injection.

Secondary Outcome Measures

Spasticity of the elbow flexors
Spasticity of the elbow flexors according to Tardieu scale at different time : Spasticity is muscle resistance during fast-moving passive stretching. It is evaluated by the Tardieu scale and it consists in studying the evolution of the muscular reaction and its angle of occurrence.The muscular reaction to the rapid stretching of the muscle is graded in 5 classes from 0 to 4
Limitation of the active movement angle 5LAMA) for elbow extension
Limitation of the active movement angle for elbow extension at different time : the subtractionof the angle of maximum elbow extension obtained during passive stretching of muscles at the maximum elbow extension angle obtained during a voluntary active contraction. As part of the protocol, the LAMA will be instrumentally measured with the 3D kinematic system.
The Fugl-Meyer Motor Function Assessment
Fugl-Meyer score at different visits : The Fugl-Meyer Motor Function Assessment, is a scale of evaluation of the reference voluntary motricity in the cerebral adult. The FMA-Motor portion of the upper limb is rated 66. It has high validity, reliability and sensitivity to change.
Functional capabilities with Wolf Motor Function Test score at different visits
Functional capabilities with WMFT score : standardized scale assessing upper limb capacities in cerebral palsy adults The scale consists of 17 standardized tests, sorted in order of increasing complexity, which solicit the proximal joints through analytical movements, and progress towards the distal joints through the execution of functional tasks of grasping, grasping and manipulating objects, evaluating single- and bimanual grips. The handover device is standardized. WMFT assesses three aspects of movement
EEG quantification of bilateral cortical activity during movement
EEG quantification of bilateral cortical activity during movement to calculate the Desynchronization index (ERD) identifying hyperactivity in the ipsilesional cortex
Cortico-spinal excitability of the motor cortex
Cortico-spinal excitability of the motor cortex assessed with TMS : TMS is a non-invasive magnetic stimulation technique that evaluates the integrity of the corticospinal tract. One of the measures used in current practice is that of the amplitude variations of a EMF collected by EMG of the surface elbow flexors as a function of stimulation intensity. The intensity curve is an index of cortical excitability.
Integrity of encephalic motor tracts
Integrity of encephalic motor tracts with an anatomic and diffusion RMI : An encephalic MRI without injection of contrast material with an anatomical sequence and a diffusion sequence will make it possible to evaluate the integrity of the motor pathways at the cortical level, the internal capsule, and the brainstem. The interest will be to evaluate the level of integrity of the cortico-spinal tract compared to other bundles, with the hypothesis that a lesion of the cortico-spinal tract favors the in play of the accessory motorways

Full Information

First Posted
December 18, 2018
Last Updated
July 21, 2023
Sponsor
University Hospital, Toulouse
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1. Study Identification

Unique Protocol Identification Number
NCT03783572
Brief Title
Upper-limb Active Function and Botulinum Toxin A
Acronym
ULAFBoT-Stroke
Official Title
Upper-limb Active Function and Botulinum Toxin A
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 8, 2020 (Actual)
Primary Completion Date
December 30, 2027 (Anticipated)
Study Completion Date
December 30, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Toulouse

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This study in an observational, prospective and longitudinal study. The aim of the study is to evaluate the effect of botulinum toxin type A (BTX) injections into the elbow flexors on the reduction of spastic co-contractions (spastic co-contraction index, SCCI) during an active elbow extension in chronic post-stroke patients.TBA injections are performed as part of routine care
Detailed Description
BTX is a valuable treatment in the management of the focal muscle overactivity (spasticity) following acquired brain injury. If BTX injections reduce spasticity, few studies have examined its effect on the improvement of active function of the upper limb. Motor task involves the muscles agonists and antagonists by phenomena of muscular coactivation. In post-stroke patients, functional cortical reorganization secondary to the phenomena of plasticity leads to a reduced motor selectivity. The increase of muscular coactivation correspond to the spastic cocontraction, which are a little evaluated in clinical practice and research, whereas they appear to have a greater impact than spasticity on limitation of active movement. This study does not evaluate the efficacy of treatment (BTX injection) but the effect of this treatment on a component of muscle hyperactivity, the spastic cocontraction. In addition to the 5 follow-up visits, patients have 6 intercurrent visits. These visits are less invasive and include only a clinical assessment with surface EMG registration. These evaluations will evaluate the efficacy and harm effect of BTX on clinical parameters and on the spastic co-contraction index. Five intercurrent visits I1, I2, I3, I4, I5 are perform respectively 2 weeks after T1 and, 3, 6, 9, 12 weeks after T2.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stroke, Muscle Spasticity, Upper Extremity Paralysis
Keywords
Botulinum toxin, Cerebrovascular Accident, upper-limb movement, spastic cocontraction, electromyography, electroencephalography

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
2 groups, one with 40 stroke patients and the control group with 40 healthy subjects prospective, longitudinal, without blinding, multicenter.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Stroke patients
Arm Type
Experimental
Arm Description
40 stroke patients : Injection of the TBA and the investigator will compare the measure of spastic cocontraction index (ICCS) during different movement before versus 4 weeks after injection of TBA : Clinical evaluation and Instrumental evaluation TBA injections are performed as part of routine care
Arm Title
Control Group
Arm Type
Active Comparator
Arm Description
The control group : Clinical evaluation consists in the search for criteria of non-inclusion and manual laterality score The will ha an Instrumental review just like the patient : concomitant evaluation of the 3D kinematics of the dominant upper limb, EMG of the triceps brachii muscles, biceps brachii, brachio-radial, brachial; associated with EEG recording, during active extension and elbow flexion movements, of the dominant upper extremity, at spontaneous and maximal speed Clinical evaluation
Intervention Type
Other
Intervention Name(s)
Clinical evaluation
Intervention Description
For the control group : only one clinical evaluation : search for non-inclusion criteria and manual laterality score
Intervention Type
Other
Intervention Name(s)
Clinical evaluation and Instrumental evaluation
Intervention Description
For the patient : The standard clinical examination to evaluate movement : pain, motive power, spasticity plus Edinburgh's laterality score and Sensitivity deficiency by the Erasmus Nottingham Sensory Assessment (EmNSA) score and the evaluation of the cognitive function An encephalic MRI An instrumental evaluation : with concomitant recording of 3D kinematic data, surface and intramuscular EMG of the flexor and elbow extensor muscles, and EEG during active elbow extension, paretic and non-paretic movements.
Primary Outcome Measure Information:
Title
Measurement of the spastic co-contraction index from the EMG signal
Description
Measurement of the spastic co-contraction index (SCCI) during a maximal active elbow extension, obtained from the EMG signal of the elbow muscles on the paretic side before / after BTX injection.
Time Frame
4 weeks
Secondary Outcome Measure Information:
Title
Spasticity of the elbow flexors
Description
Spasticity of the elbow flexors according to Tardieu scale at different time : Spasticity is muscle resistance during fast-moving passive stretching. It is evaluated by the Tardieu scale and it consists in studying the evolution of the muscular reaction and its angle of occurrence.The muscular reaction to the rapid stretching of the muscle is graded in 5 classes from 0 to 4
Time Frame
4 weeks
Title
Limitation of the active movement angle 5LAMA) for elbow extension
Description
Limitation of the active movement angle for elbow extension at different time : the subtractionof the angle of maximum elbow extension obtained during passive stretching of muscles at the maximum elbow extension angle obtained during a voluntary active contraction. As part of the protocol, the LAMA will be instrumentally measured with the 3D kinematic system.
Time Frame
4 weeks
Title
The Fugl-Meyer Motor Function Assessment
Description
Fugl-Meyer score at different visits : The Fugl-Meyer Motor Function Assessment, is a scale of evaluation of the reference voluntary motricity in the cerebral adult. The FMA-Motor portion of the upper limb is rated 66. It has high validity, reliability and sensitivity to change.
Time Frame
4 weeks
Title
Functional capabilities with Wolf Motor Function Test score at different visits
Description
Functional capabilities with WMFT score : standardized scale assessing upper limb capacities in cerebral palsy adults The scale consists of 17 standardized tests, sorted in order of increasing complexity, which solicit the proximal joints through analytical movements, and progress towards the distal joints through the execution of functional tasks of grasping, grasping and manipulating objects, evaluating single- and bimanual grips. The handover device is standardized. WMFT assesses three aspects of movement
Time Frame
4 weeks
Title
EEG quantification of bilateral cortical activity during movement
Description
EEG quantification of bilateral cortical activity during movement to calculate the Desynchronization index (ERD) identifying hyperactivity in the ipsilesional cortex
Time Frame
4 weeks
Title
Cortico-spinal excitability of the motor cortex
Description
Cortico-spinal excitability of the motor cortex assessed with TMS : TMS is a non-invasive magnetic stimulation technique that evaluates the integrity of the corticospinal tract. One of the measures used in current practice is that of the amplitude variations of a EMF collected by EMG of the surface elbow flexors as a function of stimulation intensity. The intensity curve is an index of cortical excitability.
Time Frame
4 weeks
Title
Integrity of encephalic motor tracts
Description
Integrity of encephalic motor tracts with an anatomic and diffusion RMI : An encephalic MRI without injection of contrast material with an anatomical sequence and a diffusion sequence will make it possible to evaluate the integrity of the motor pathways at the cortical level, the internal capsule, and the brainstem. The interest will be to evaluate the level of integrity of the cortico-spinal tract compared to other bundles, with the hypothesis that a lesion of the cortico-spinal tract favors the in play of the accessory motorways
Time Frame
4 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Stroke group : Inclusion Criteria: Cortical and/or subcortical ischemic or haemorrhagic stroke for at least 6 months; Indication to an injection of BTA in the elbow flexor muscles according to the usual clinical criteria: request of elbow extension improvement with a functional or aesthetic objective; Being under prescription of abobotulinum toxin A (DYSPORT®, Ipsen-Pharma); Ability of active elbow extension> 20 degrees; Limitation of active movement of elbow extension > 15 degrees or decreased or 50% decrease in the active elbow extension rate; Patients who have never been treated with BTX or only a first injection that having targeted the elbow flexors more than 4 months ago; Age> 18 years; Signature of informed consent; Subject affiliated to the social security coverture. Exclusion Criteria: Passive limitation of elbow extension > 30 degrees; Pain during active movements of elbow flexion/extension; Cognitive disorder with limited comprehension of three basic instructions (like the test of the 3 papers of the MMS); Evolutionary or decompensated neurological disease; Unstabilized epilepsy; Anticoagulant treatment with a curative dose or hemostasis disorder that contraindicates intramuscular injections; Claustrophobia or metallic foreign bodies contraindicated for MRI; General contraindication for botulinum toxin injection: hypersensitivity to the active substance or to one of the excipients, swallowing disorder, chronic respiratory disorders, antecedent of myasthenia or Lambert Eaton syndrome; antecedent of neuromuscular disease; surgery with curarization for less than a month; current treatment with aminoglycoside, aminoquinoline, cyclosporine or anticholinesterase. Presence of skin infection or inflammation at the injection site. Legal incapacity. Pregnant or breastfeeding woman; Woman with a desire to become pregnant within 18 months. Non-menopausal woman (a postmenopausal state is defined as no menses for 12 months without an alternative medical cause) who does not use one of the following contraceptive methods considered highly effective : intrauterine device, oestroprogestonic contraception or progestogen hormonal contraception associated with inhibition of ovulation, intrauterine hormone-releasing system, or bilateral tubal occlusion. Control group inclusion criteria: Age> 18 years Signature of informed consent. exclusion criteria: History of orthopedic or neurologic disorders; Subject expert in a sport intensively requiring the upper limbs (at least departmental competition level); Legal incapacity.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
David Gasq, MD
Phone
05 61 32 28 42
Ext
33
Email
gasq.d@chu-toulouse.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Audrey Tomasik
Phone
05 61 77 85 97
Ext
33
Email
tomasik.a@chu-toulouse.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Gasq, MD
Organizational Affiliation
University Hospital, Toulouse
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospital Toulouse
City
Toulouse
ZIP/Postal Code
31059
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
David Gasq, MD
Phone
05 61 32 28 42
Ext
33
Email
gasq.d@chu-toulouse.fr
First Name & Middle Initial & Last Name & Degree
Audrey TOMASIK
Phone
05 61 77 85 97
Ext
33
Email
tomasik.a@chu-toulouse.fr

12. IPD Sharing Statement

Plan to Share IPD
No

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Upper-limb Active Function and Botulinum Toxin A

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