<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/NCT03044080</url>
  </required_header>
  <id_info>
    <org_study_id>PSM/RHB/NR22</org_study_id>
    <nct_id>NCT03044080</nct_id>
  </id_info>
  <brief_title>Effects of Botulinum Neurotoxin Type A (BoNT/A) Free of Complexing Proteins in the Spastic Equinovarus Foot</brief_title>
  <official_title>Effects of Repeated Use of Botulinum Neurotoxin Type A (BoNT/A) Free of Complexing Proteins in the Spastic Equinovarus Foot in Stroke Patients: A Randomized Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Parc de Salut Mar</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Parc de Salut Mar</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>
      Clinical randomized clinical trial to assess the effectiveness on walking speed of repeated&#xD;
      use of botulinum neurotoxin type A (BoNT/A)in the post-stroke spastic equinovarus foot in&#xD;
      three successive infiltrations at 6-month intervals, checking if the sustainability of the&#xD;
      effect is greater in incobotulinumtoxin A (Xeomin®) than in onabotulinumtoxinA (Botox®).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Spasticity is present in 38% of patients at six months after stroke. Equinovarus foot, with&#xD;
      or without claw toes and striatal foot, is especially common. There is a weak to moderate&#xD;
      evidence in favor of the use of botulinum neurotoxin type A (BoNT/A) in the equinovarus foot,&#xD;
      stiff-knee and in other patterns that may interfere with gait ability. Specifically, BoNT/A&#xD;
      increases walking speed in stroke patients with spastic equinovarus foot.&#xD;
&#xD;
      Repeated use of BoNT/A may lead to the appearance of neutralizing antibodies, so its effect&#xD;
      may decrease over successive infiltrations. Among the differential characteristics of&#xD;
      incobotulinumtoxinA (Xeomin®) there is a reduced inactivated botulinum neurotoxin content and&#xD;
      the lack of complexing proteins, which would diminish antigenicity and not suppose a decrease&#xD;
      of the effect before successive infiltrations.&#xD;
&#xD;
      The objective of this project is to determine the effect on walking speed of repeated use of&#xD;
      BoNT/A in post-stroke spinal equinovarus foot in three consecutive injections at 6-month&#xD;
      intervals and to investigate whether the sustainability of the effect is greater in&#xD;
      incobotulinumtoxinA (Xeomin®) than in onabotulinumtoxinA (Botox®). All patients will receive&#xD;
      200-300 units of BoNT/A (Xeomin ® or Botox ®) that will be distributed according to the&#xD;
      individual clinical pattern of spastic equinovarus foot.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 1, 2015</start_date>
  <completion_date type="Actual">September 30, 2017</completion_date>
  <primary_completion_date type="Actual">June 30, 2017</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Parallel assignment</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
    <masking_description>Double blind</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change in walking speed</measure>
    <time_frame>Baseline and monthly during 18 months</time_frame>
    <description>Walking speed, expressed in m/s, is assessed in a 10-m corridor</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in spasticity assessed with the Modified Ashworth Scale</measure>
    <time_frame>Baseline and monthly during 18 months</time_frame>
    <description>Spasticity assessed with the Modified Ashworth Scale (range 0-5)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in walking disability assessed with the Scandinavian Stroke Scale</measure>
    <time_frame>Baseline and monthly during 18 months</time_frame>
    <description>Walking disability is assessed with the Scandinavian Stroke Scale</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in functional ambulation ability assessed with the Modified Walking Categories</measure>
    <time_frame>Baseline and monthly during 18 months</time_frame>
    <description>Functional ambulation ability is assessed with the Modified Walking Categories</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in step time</measure>
    <time_frame>Baseline and monthly during 18 months</time_frame>
    <description>Step time (Temporal gait parameter) is expressed in seconds and assessed with instrumented gait analysis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in step length</measure>
    <time_frame>Baseline and monthly during 18 months</time_frame>
    <description>Step length (Spatial gait parameter) is expressed in meters and assessed with instrumented gait analysis</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Stroke Rehabilitation</condition>
  <condition>Stroke Rehabilitation Spasticity Management</condition>
  <arm_group>
    <arm_group_label>IncobotulinumtoxinA</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Injection of 200-300 units of IncobotulinumtoxinA (Xeomin ®)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>OnabotulinumtoxinA</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Injection of 200-300 units of onabotulinumtoxiA (Botox®)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>IncobotulinumtoxinA</intervention_name>
    <description>Three consecutive injections of 200-300 units of IncobotulinumtoxinA (Xeomin ®) under ultrasound guidance. The IncobotulinumtoxinA will be distributed according to the individual clinical pattern of spasticity: plantar flexor muscles (triceps sural: gastrocnemius and soleus), tibialis posterior, flexor digitorum longus.</description>
    <arm_group_label>IncobotulinumtoxinA</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>OnabotulinumtoxinA</intervention_name>
    <description>ree consecutive injections of 200-300 units of OnabotulinumtoxinA (Botox ®) under ultrasound guidance. The BoNT/A will be distributed according to the individual clinical pattern of spasticity: plantar flexor muscles (triceps sural: gastrocnemius and soleus), tibialis posterior, flexor digitorum longus.</description>
    <arm_group_label>OnabotulinumtoxinA</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  First-ever Ischemic or haemorrhagic stroke&#xD;
&#xD;
          -  Time since stroke onset: &gt;6months&#xD;
&#xD;
          -  Hemiparesis with equinovarus foot&#xD;
&#xD;
          -  No previous BoNT/A&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Non-ambulant patients&#xD;
&#xD;
          -  Medical contraindications for BoNT/A use that appear in the product information sheet&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Esther Duarte, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fundació IMIM - Parc de Salut Mar</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hospital de l'Esperança</name>
      <address>
        <city>Barcelona</city>
        <zip>08024</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <reference>
    <citation>Sommerfeld DK, Eek EU, Svensson AK, Holmqvist LW, von Arbin MH. Spasticity after stroke: its occurrence and association with motor impairments and activity limitations. Stroke. 2004 Jan;35(1):134-9. doi: 10.1161/01.STR.0000105386.05173.5E. Epub 2003 Dec 18.</citation>
    <PMID>14684785</PMID>
  </reference>
  <reference>
    <citation>Watkins CL, Leathley MJ, Gregson JM, Moore AP, Smith TL, Sharma AK. Prevalence of spasticity post stroke. Clin Rehabil. 2002 Aug;16(5):515-22. doi: 10.1191/0269215502cr512oa.</citation>
    <PMID>12194622</PMID>
  </reference>
  <reference>
    <citation>Foley N, Murie-Fernandez M, Speechley M, Salter K, Sequeira K, Teasell R. Does the treatment of spastic equinovarus deformity following stroke with botulinum toxin increase gait velocity? A systematic review and meta-analysis. Eur J Neurol. 2010 Dec;17(12):1419-27. doi: 10.1111/j.1468-1331.2010.03084.x.</citation>
    <PMID>20491885</PMID>
  </reference>
  <reference>
    <citation>Dressler D. Five-year experience with incobotulinumtoxinA (Xeomin((R)) ): the first botulinum toxin drug free of complexing proteins. Eur J Neurol. 2012 Mar;19(3):385-9. doi: 10.1111/j.1468-1331.2011.03559.x. Epub 2011 Oct 28.</citation>
    <PMID>22035051</PMID>
  </reference>
  <verification_date>February 2017</verification_date>
  <study_first_submitted>February 1, 2017</study_first_submitted>
  <study_first_submitted_qc>February 3, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">February 6, 2017</study_first_posted>
  <last_update_submitted>October 19, 2017</last_update_submitted>
  <last_update_submitted_qc>October 19, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">October 20, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Parc de Salut Mar</investigator_affiliation>
    <investigator_full_name>Esther Duarte</investigator_full_name>
    <investigator_title>Rehabilitation Research Group Coordinator, PhD</investigator_title>
  </responsible_party>
  <keyword>Walking Disorder</keyword>
  <keyword>Stroke</keyword>
  <keyword>Botulinum Toxin</keyword>
  <keyword>Spasticity</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Muscle Spasticity</mesh_term>
    <mesh_term>Clubfoot</mesh_term>
    <mesh_term>Stroke</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Botulinum Toxins, Type A</mesh_term>
    <mesh_term>incobotulinumtoxinA</mesh_term>
    <mesh_term>abobotulinumtoxinA</mesh_term>
  </intervention_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/NCT03044080
org study id: PSM/RHB/NR22
nct id: NCT03044080
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Clinical randomized clinical trial to assess the effectiveness on walking speed of repeated
      use of botulinum neurotoxin type A (BoNT/A)in the post-stroke spastic equinovarus foot in
      three successive infiltrations at 6-month intervals, checking if the sustainability of the
      effect is greater in incobotulinumtoxin A (Xeomin®) than in onabotulinumtoxinA (Botox®).
Spasticity is present in 38% of patients at six months after stroke. Equinovarus foot, with
      or without claw toes and striatal foot, is especially common. There is a weak to moderate
      evidence in favor of the use of botulinum neurotoxin type A (BoNT/A) in the equinovarus foot,
      stiff-knee and in other patterns that may interfere with gait ability. Specifically, BoNT/A
      increases walking speed in stroke patients with spastic equinovarus foot.

      Repeated use of BoNT/A may lead to the appearance of neutralizing antibodies, so its effect
      may decrease over successive infiltrations. Among the differential characteristics of
      incobotulinumtoxinA (Xeomin®) there is a reduced inactivated botulinum neurotoxin content and
      the lack of complexing proteins, which would diminish antigenicity and not suppose a decrease
      of the effect before successive infiltrations.

      The objective of this project is to determine the effect on walking speed of repeated use of
      BoNT/A in post-stroke spinal equinovarus foot in three consecutive injections at 6-month
      intervals and to investigate whether the sustainability of the effect is greater in
      incobotulinumtoxinA (Xeomin®) than in onabotulinumtoxinA (Botox®). All patients will receive
      200-300 units of BoNT/A (Xeomin ® or Botox ®) that will be distributed according to the
      individual clinical pattern of spastic equinovarus foot.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Parallel assignment
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
masking description: Double blind
measure: Change in walking speed
time frame: Baseline and monthly during 18 months
description: Walking speed, expressed in m/s, is assessed in a 10-m corridor
measure: Change in spasticity assessed with the Modified Ashworth Scale
time frame: Baseline and monthly during 18 months
description: Spasticity assessed with the Modified Ashworth Scale (range 0-5)
measure: Change in walking disability assessed with the Scandinavian Stroke Scale
time frame: Baseline and monthly during 18 months
description: Walking disability is assessed with the Scandinavian Stroke Scale
measure: Change in functional ambulation ability assessed with the Modified Walking Categories
time frame: Baseline and monthly during 18 months
description: Functional ambulation ability is assessed with the Modified Walking Categories
measure: Change in step time
time frame: Baseline and monthly during 18 months
description: Step time (Temporal gait parameter) is expressed in seconds and assessed with instrumented gait analysis
measure: Change in step length
time frame: Baseline and monthly during 18 months
description: Step length (Spatial gait parameter) is expressed in meters and assessed with instrumented gait analysis
arm group label: IncobotulinumtoxinA
arm group type: Active Comparator
description: Injection of 200-300 units of IncobotulinumtoxinA (Xeomin ®)
arm group label: OnabotulinumtoxinA
arm group type: Active Comparator
description: Injection of 200-300 units of onabotulinumtoxiA (Botox®)
intervention type: Drug
intervention name: IncobotulinumtoxinA
description: Three consecutive injections of 200-300 units of IncobotulinumtoxinA (Xeomin ®) under ultrasound guidance. The IncobotulinumtoxinA will be distributed according to the individual clinical pattern of spasticity: plantar flexor muscles (triceps sural: gastrocnemius and soleus), tibialis posterior, flexor digitorum longus.
arm group label: IncobotulinumtoxinA
intervention type: Drug
intervention name: OnabotulinumtoxinA
description: ree consecutive injections of 200-300 units of OnabotulinumtoxinA (Botox ®) under ultrasound guidance. The BoNT/A will be distributed according to the individual clinical pattern of spasticity: plantar flexor muscles (triceps sural: gastrocnemius and soleus), tibialis posterior, flexor digitorum longus.
arm group label: OnabotulinumtoxinA
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Esther Duarte, PhD
role: Principal Investigator
affiliation: Fundació IMIM - Parc de Salut Mar
facility: 
country: Spain
citation: Sommerfeld DK, Eek EU, Svensson AK, Holmqvist LW, von Arbin MH. Spasticity after stroke: its occurrence and association with motor impairments and activity limitations. Stroke. 2004 Jan;35(1):134-9. doi: 10.1161/01.STR.0000105386.05173.5E. Epub 2003 Dec 18.
PMID: 14684785
citation: Watkins CL, Leathley MJ, Gregson JM, Moore AP, Smith TL, Sharma AK. Prevalence of spasticity post stroke. Clin Rehabil. 2002 Aug;16(5):515-22. doi: 10.1191/0269215502cr512oa.
PMID: 12194622
citation: Foley N, Murie-Fernandez M, Speechley M, Salter K, Sequeira K, Teasell R. Does the treatment of spastic equinovarus deformity following stroke with botulinum toxin increase gait velocity? A systematic review and meta-analysis. Eur J Neurol. 2010 Dec;17(12):1419-27. doi: 10.1111/j.1468-1331.2010.03084.x.
PMID: 20491885
citation: Dressler D. Five-year experience with incobotulinumtoxinA (Xeomin((R)) ): the first botulinum toxin drug free of complexing proteins. Eur J Neurol. 2012 Mar;19(3):385-9. doi: 10.1111/j.1468-1331.2011.03559.x. Epub 2011 Oct 28.
PMID: 22035051
responsible party type: Principal Investigator
investigator affiliation: Parc de Salut Mar
investigator full name: Esther Duarte
investigator title: Rehabilitation Research Group Coordinator, PhD
mesh term: Muscle Spasticity
mesh term: Clubfoot
mesh term: Stroke
mesh term: Botulinum Toxins, Type A
mesh term: incobotulinumtoxinA
mesh term: abobotulinumtoxinA
sharing ipd: No