<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03783572</url>
  </required_header>
  <id_info>
    <org_study_id>RC31/17/0455</org_study_id>
    <secondary_id>2018-000941-38</secondary_id>
    <nct_id>NCT03783572</nct_id>
  </id_info>
  <brief_title>Upper-limb Active Function and Botulinum Toxin A</brief_title>
  <acronym>ULAFBoT-Stroke</acronym>
  <official_title>Upper-limb Active Function and Botulinum Toxin A</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Toulouse</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital, Toulouse</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study in an observational, prospective and longitudinal study. The aim of the study is&#xD;
      to evaluate the effect of botulinum toxin type A (BTX) injections into the elbow flexors on&#xD;
      the reduction of spastic co-contractions (spastic co-contraction index, SCCI) during an&#xD;
      active elbow extension in chronic post-stroke patients.TBA injections are performed as part&#xD;
      of routine care&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      BTX is a valuable treatment in the management of the focal muscle overactivity (spasticity)&#xD;
      following acquired brain injury. If BTX injections reduce spasticity, few studies have&#xD;
      examined its effect on the improvement of active function of the upper limb.&#xD;
&#xD;
      Motor task involves the muscles agonists and antagonists by phenomena of muscular&#xD;
      coactivation.&#xD;
&#xD;
      In post-stroke patients, functional cortical reorganization secondary to the phenomena of&#xD;
      plasticity leads to a reduced motor selectivity. The increase of muscular coactivation&#xD;
      correspond to the spastic cocontraction, which are a little evaluated in clinical practice&#xD;
      and research, whereas they appear to have a greater impact than spasticity on limitation of&#xD;
      active movement.&#xD;
&#xD;
      This study does not evaluate the efficacy of treatment (BTX injection) but the effect of this&#xD;
      treatment on a component of muscle hyperactivity, the spastic cocontraction.&#xD;
&#xD;
      In addition to the 5 follow-up visits, patients have 6 intercurrent visits. These visits are&#xD;
      less invasive and include only a clinical assessment with surface EMG registration. These&#xD;
      evaluations will evaluate the efficacy and harm effect of BTX on clinical parameters and on&#xD;
      the spastic co-contraction index. Five intercurrent visits I1, I2, I3, I4, I5 are perform&#xD;
      respectively 2 weeks after T1 and, 3, 6, 9, 12 weeks after T2.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">December 8, 2020</start_date>
  <completion_date type="Anticipated">December 30, 2027</completion_date>
  <primary_completion_date type="Anticipated">December 30, 2027</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>2 groups, one with 40 stroke patients and the control group with 40 healthy subjects prospective, longitudinal, without blinding, multicenter.</intervention_model_description>
    <primary_purpose>Supportive Care</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Measurement of the spastic co-contraction index from the EMG signal</measure>
    <time_frame>4 weeks</time_frame>
    <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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Spasticity of the elbow flexors</measure>
    <time_frame>4 weeks</time_frame>
    <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</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Limitation of the active movement angle 5LAMA) for elbow extension</measure>
    <time_frame>4 weeks</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Fugl-Meyer Motor Function Assessment</measure>
    <time_frame>4 weeks</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Functional capabilities with Wolf Motor Function Test score at different visits</measure>
    <time_frame>4 weeks</time_frame>
    <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</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>EEG quantification of bilateral cortical activity during movement</measure>
    <time_frame>4 weeks</time_frame>
    <description>EEG quantification of bilateral cortical activity during movement to calculate the Desynchronization index (ERD) identifying hyperactivity in the ipsilesional cortex</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cortico-spinal excitability of the motor cortex</measure>
    <time_frame>4 weeks</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Integrity of encephalic motor tracts</measure>
    <time_frame>4 weeks</time_frame>
    <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.&#xD;
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</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">80</enrollment>
  <condition>Stroke</condition>
  <condition>Muscle Spasticity</condition>
  <condition>Upper Extremity Paralysis</condition>
  <arm_group>
    <arm_group_label>Stroke patients</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <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</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control Group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <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</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Clinical evaluation</intervention_name>
    <description>For the control group : only one clinical evaluation : search for non-inclusion criteria and manual laterality score</description>
    <arm_group_label>Control Group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Clinical evaluation and Instrumental evaluation</intervention_name>
    <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.</description>
    <arm_group_label>Stroke patients</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Stroke group :&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          -  Cortical and/or subcortical ischemic or haemorrhagic stroke for at least 6 months;&#xD;
&#xD;
          -  Indication to an injection of BTA in the elbow flexor muscles according to the usual&#xD;
             clinical criteria: request of elbow extension improvement with a functional or&#xD;
             aesthetic objective;&#xD;
&#xD;
          -  Being under prescription of abobotulinum toxin A (DYSPORT®, Ipsen-Pharma);&#xD;
&#xD;
          -  Ability of active elbow extension&gt; 20 degrees;&#xD;
&#xD;
          -  Limitation of active movement of elbow extension &gt; 15 degrees or decreased or 50%&#xD;
             decrease in the active elbow extension rate;&#xD;
&#xD;
          -  Patients who have never been treated with BTX or only a first injection that having&#xD;
             targeted the elbow flexors more than 4 months ago;&#xD;
&#xD;
          -  Age&gt; 18 years;&#xD;
&#xD;
          -  Signature of informed consent;&#xD;
&#xD;
          -  Subject affiliated to the social security coverture.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Passive limitation of elbow extension &gt; 30 degrees;&#xD;
&#xD;
          -  Pain during active movements of elbow flexion/extension;&#xD;
&#xD;
          -  Cognitive disorder with limited comprehension of three basic instructions (like the&#xD;
             test of the 3 papers of the MMS);&#xD;
&#xD;
          -  Evolutionary or decompensated neurological disease;&#xD;
&#xD;
          -  Unstabilized epilepsy;&#xD;
&#xD;
          -  Anticoagulant treatment with a curative dose or hemostasis disorder that&#xD;
             contraindicates intramuscular injections;&#xD;
&#xD;
          -  Claustrophobia or metallic foreign bodies contraindicated for MRI;&#xD;
&#xD;
          -  General contraindication for botulinum toxin injection: hypersensitivity to the active&#xD;
             substance or to one of the excipients, swallowing disorder, chronic respiratory&#xD;
             disorders, antecedent of myasthenia or Lambert Eaton syndrome; antecedent of&#xD;
             neuromuscular disease; surgery with curarization for less than a month; current&#xD;
             treatment with aminoglycoside, aminoquinoline, cyclosporine or anticholinesterase.&#xD;
&#xD;
          -  Presence of skin infection or inflammation at the injection site.&#xD;
&#xD;
          -  Legal incapacity.&#xD;
&#xD;
          -  Pregnant or breastfeeding woman;&#xD;
&#xD;
          -  Woman with a desire to become pregnant within 18 months.&#xD;
&#xD;
          -  Non-menopausal woman (a postmenopausal state is defined as no menses for 12 months&#xD;
             without an alternative medical cause) who does not use one of the following&#xD;
             contraceptive methods considered highly effective : intrauterine device,&#xD;
             oestroprogestonic contraception or progestogen hormonal contraception associated with&#xD;
             inhibition of ovulation, intrauterine hormone-releasing system, or bilateral tubal&#xD;
             occlusion.&#xD;
&#xD;
        Control group&#xD;
&#xD;
          -  inclusion criteria:&#xD;
&#xD;
               -  Age&gt; 18 years&#xD;
&#xD;
               -  Signature of informed consent.&#xD;
&#xD;
          -  exclusion criteria:&#xD;
&#xD;
               -  History of orthopedic or neurologic disorders;&#xD;
&#xD;
               -  Subject expert in a sport intensively requiring the upper limbs (at least&#xD;
                  departmental competition level);&#xD;
&#xD;
               -  Legal incapacity.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>David Gasq, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital, Toulouse</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>David Gasq, MD</last_name>
    <phone>05 61 32 28 42</phone>
    <phone_ext>33</phone_ext>
    <email>gasq.d@chu-toulouse.fr</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Audrey Tomasik</last_name>
    <phone>05 61 77 85 97</phone>
    <phone_ext>33</phone_ext>
    <email>tomasik.a@chu-toulouse.fr</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>University Hospital Toulouse</name>
      <address>
        <city>Toulouse</city>
        <zip>31059</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>David Gasq, MD</last_name>
      <phone>05 61 32 28 42</phone>
      <phone_ext>33</phone_ext>
      <email>gasq.d@chu-toulouse.fr</email>
    </contact>
    <contact_backup>
      <last_name>Audrey TOMASIK</last_name>
      <phone>05 61 77 85 97</phone>
      <phone_ext>33</phone_ext>
      <email>tomasik.a@chu-toulouse.fr</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>December 18, 2018</study_first_submitted>
  <study_first_submitted_qc>December 18, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 21, 2018</study_first_posted>
  <last_update_submitted>July 21, 2023</last_update_submitted>
  <last_update_submitted_qc>July 21, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 24, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Botulinum toxin</keyword>
  <keyword>Cerebrovascular Accident</keyword>
  <keyword>upper-limb movement</keyword>
  <keyword>spastic cocontraction</keyword>
  <keyword>electromyography</keyword>
  <keyword>electroencephalography</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Muscle Spasticity</mesh_term>
    <mesh_term>Paralysis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03783572
org study id: RC31/17/0455
secondary id: 2018-000941-38
nct id: NCT03783572
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
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
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.
allocation: Non-Randomized
intervention model: Parallel Assignment
intervention model description: 2 groups, one with 40 stroke patients and the control group with 40 healthy subjects prospective, longitudinal, without blinding, multicenter.
primary purpose: Supportive Care
masking: None (Open Label)
measure: Measurement of the spastic co-contraction index from the EMG signal
time frame: 4 weeks
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.
measure: Spasticity of the elbow flexors
time frame: 4 weeks
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
measure: Limitation of the active movement angle 5LAMA) for elbow extension
time frame: 4 weeks
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.
measure: The Fugl-Meyer Motor Function Assessment
time frame: 4 weeks
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.
measure: Functional capabilities with Wolf Motor Function Test score at different visits
time frame: 4 weeks
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
measure: EEG quantification of bilateral cortical activity during movement
time frame: 4 weeks
description: EEG quantification of bilateral cortical activity during movement to calculate the Desynchronization index (ERD) identifying hyperactivity in the ipsilesional cortex
measure: Cortico-spinal excitability of the motor cortex
time frame: 4 weeks
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.
measure: Integrity of encephalic motor tracts
time frame: 4 weeks
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
arm group label: Stroke patients
arm group type: Experimental
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 group label: Control Group
arm group type: Active Comparator
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: Clinical evaluation
description: For the control group : only one clinical evaluation : search for non-inclusion criteria and manual laterality score
arm group label: Control Group
intervention type: Other
intervention name: Clinical evaluation and Instrumental evaluation
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.
arm group label: Stroke patients
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: David Gasq, MD
role: Principal Investigator
affiliation: University Hospital, Toulouse
last name: David Gasq, MD
phone: 05 61 32 28 42
phone ext: 33
email: gasq.d@chu-toulouse.fr
last name: Audrey Tomasik
phone: 05 61 77 85 97
phone ext: 33
email: tomasik.a@chu-toulouse.fr
facility: 
status: Recruiting
contact: 
contact backup: 
country: France
responsible party type: Sponsor
mesh term: Muscle Spasticity
mesh term: Paralysis
sharing ipd: No