<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/NCT04448483</url>
  </required_header>
  <id_info>
    <org_study_id>AVANCER</org_study_id>
    <nct_id>NCT04448483</nct_id>
  </id_info>
  <brief_title>Clinical Study for Upper Limb Motor Restoration in Chronic Stroke Patients Using Personalized Neuro-technologies</brief_title>
  <acronym>AVANCER</acronym>
  <official_title>Accident Vasculaire cérébral et Apport Des Neurotechnologies individualisées Chez la Personne Avec Une hémiparésie Chronique : Une Etude Clinique Prospective Visant à Restaurer la mobilité du Membre supérieur</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Wyss Center for Bio and Neuroengineering</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Ecole Polytechnique Fédérale de Lausanne</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Wyss Center for Bio and Neuroengineering</source>
  <oversight_info>
    <has_dmc>Yes</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 aims to evaluate safety, tolerability and efficacy of a new treatment for upper&#xD;
      limb motor rehabilitation after severe stroke using non-invasive neurotechnologies. The&#xD;
      investigational system is used alone or coupled with brain stimulation provided by&#xD;
      transcranic direct current stimulation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study aims at providing two interventions:&#xD;
&#xD;
      In the first intervention, a brain computer interface able to non-invasively detect motor&#xD;
      intention from the non-invasive measure of brain activity by using electroencephalography&#xD;
      (BrainVision, V-amp) activates a robotic glove (Gloreha Sinfonia, Idrogenet Srl) that will&#xD;
      assist-as-needed hand movements and paretic upper limb functional electric stimulation&#xD;
      (RehaStim, Hasomed). The latter will activate upper limb muscles to perform motor&#xD;
      rehabilitation exercises for the upper limb. The motor rehabilitation exercises include upper&#xD;
      limb and hand mobilization and functional tasks, such as hand open/closing, wrist&#xD;
      flexion/extension, and reach and grasp a cup, keep and release.&#xD;
&#xD;
      In the second intervention, non-invasive brain stimulation (DC-Stimulator, NeuroConn) in the&#xD;
      form of transcranial direct current stimulation will be provided in addition to the previous&#xD;
      intervention.&#xD;
&#xD;
      Each participant will perform a minimum of 11 rehabilitative sessions for the first&#xD;
      intervention and a minimum of 11 rehabilitative sessions for the second intervention, for a&#xD;
      total minimum of 22 rehabilitative sessions. If the participant recovers with the&#xD;
      intervention, the relative rehabilitative session continues to be proposed until patients&#xD;
      will reaches a &quot;plateau&quot;. The intervention will switch from 1 to 2 if the participant does&#xD;
      not improve anymore with the 1st intervention. If the patient does not improve anymore with&#xD;
      the 2nd intervention the interventional part of the trial will be finished. The&#xD;
      intervention(s) will terminate also if the participant continues to progress after 6 months&#xD;
      of inclusion. As the study is especially designed for personalization of intervention for&#xD;
      every patient, it is not possible to determine a priori the number of sessions for each&#xD;
      participant, because they depend on the response of each participant to the intervention. The&#xD;
      duration of each rehabilitative visit is about two and half hours.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">October 6, 2020</start_date>
  <completion_date type="Anticipated">December 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2023</primary_completion_date>
  <phase>N/A</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>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in functional improvement of upper limbs along training sessions</measure>
    <time_frame>10 months average</time_frame>
    <description>Measurement of improvement before and after training of upper limb, using Fugl-Meyer (FMA) scale (0-66).&#xD;
FMA is a stroke specific index to estimate motor function. Measurements are performed every second training session and at the evaluation visit.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in speed and coordination of the affected side</measure>
    <time_frame>10 months average</time_frame>
    <description>Measurement of speed and coordination of the affected side are performed using FMA modified score, max 54.&#xD;
Measurements are performed every second training session.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in sensorimotor status in the two upper limbs</measure>
    <time_frame>10 months average</time_frame>
    <description>Measurement of sensorimotor status in the two upper limbs, using Fugl-Meyer (FMA) scale (0-66).&#xD;
Measurements are performed at the evaluation visit.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Action Reach Arm Test (ARAT)</measure>
    <time_frame>10 months average</time_frame>
    <description>Upper limb functions changes measured by the ARAT test (ARAT scale: 0-57) in the two upper limbs.&#xD;
Measurements are performed at the evaluation visit.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Fatigue Visual Analog Scale (VAS)</measure>
    <time_frame>10 months average</time_frame>
    <description>Measurement of fatigue is made with the Visual Analog Scale (VAS; 0-100). Measurements are performed every second training session.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Rivermead Assessment of Somatosensory Performance (RASP)</measure>
    <time_frame>10 months average</time_frame>
    <description>Somatosensory function are measured with RASP (RASP; 0-210) in the two upper limbs.&#xD;
Measurements are performed at the evaluation visit.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Brain stimulation effectiveness in BCI-aided motor therapy</measure>
    <time_frame>10 months average</time_frame>
    <description>The measurement of the effectiveness of brain stimulation is measured by FMA scores of all patients at initial, inter-intervention and final evaluation. This measurement is made between the end and the beginning of each intervention for each patient.&#xD;
Comparison is made by using one-way ANOVA if data normally distributed, or Kruskal Wallis test if otherwise. Secondary analysis measures are calculated for each patient once they complete the study. It will consist in the evaluation of effectiveness of BCI-aided motor therapy without and with brain stimulation. Group comparison is done with inferential statistics for full and partial populations. Similar comparisons and judgement criteria are applied for clinical scales and questionnaires.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Stroke, Cerebral</condition>
  <arm_group>
    <arm_group_label>Group A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients belonging to group A will start intervention I, immediately after baseline. We will recruit about 25 for group A (randomization will take into account the two to one study design) in order to have about 20 patients in Group A that will complete the study.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients belonging to group B will follow an observation period (max. 3 months) before starting intervention I. We will recruit about 15 patients for group B (randomization will take into account the two to one study design) in order to have about 10 patients in Group B that will complete the study.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Paretic upper limb functional electric stimulation through RehaStim</intervention_name>
    <description>The stimulation will activate upper limb muscles to perform motor rehabilitation exercises for the upper limb with the help of the Gloreha Sinfonia robotic glove that will assist-as-needed hands movements. Motor intention will be detected by a BCI (Brain Computer Interface) from the non-invasive measure of brain activity by using electroencephalography.&#xD;
The motor rehabilitation exercises include upper limb and hand mobilization and functional tasks, such as hand open/closing, wrist flexion/extension, and reach and grasp a cup, keep and release.</description>
    <arm_group_label>Group A</arm_group_label>
    <arm_group_label>Group B</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Non-invasive transcranial current stimulation through DC-Stimulator</intervention_name>
    <description>Non-invasive brain stimulation in the form of transcranial direct current stimulation will be provided in addition to the previous intervention.</description>
    <arm_group_label>Group A</arm_group_label>
    <arm_group_label>Group B</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Chronic cerebral stroke patients (at least 6 months after the event).&#xD;
&#xD;
          -  First ever clinical manifest stroke.&#xD;
&#xD;
          -  No or minimal residual voluntary finger extension.&#xD;
&#xD;
          -  Upper limb FM score &lt; 20.&#xD;
&#xD;
          -  Age &gt; 18 years.&#xD;
&#xD;
          -  Right or left severe hemiparesis.&#xD;
&#xD;
          -  Ischemic or hemorrhagic stroke with intact hand knob area.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patient with an active implantable device or wearing an active device.&#xD;
&#xD;
          -  Occurrence of new clinically manifest stroke.&#xD;
&#xD;
          -  Cerebellar stroke.&#xD;
&#xD;
          -  Drug or alcohol dependency.&#xD;
&#xD;
          -  Pregnancy.&#xD;
&#xD;
          -  Refusal to perform any proposed pregnancy test for women in childbearing age (18 to&#xD;
             menopausal age).&#xD;
&#xD;
          -  Psychotic symptoms and significant psychopharmacologic treatments with neuroleptics&#xD;
             and/or Lithium and antiepileptics&#xD;
&#xD;
          -  Use of medication that significantly interacts with non-invasive brain stimulation&#xD;
             being benzodiazepines, tricyclic antidepressant and antipsychotics.&#xD;
&#xD;
          -  Severe spasticity that prevent the patient to use the robotic orthosis (indicative&#xD;
             Modified Ashworth Scale &gt; 3).&#xD;
&#xD;
          -  Severe cognitive problems and severe neglect.&#xD;
&#xD;
          -  Physical features impeding the recording of brain signals or the muscular signals&#xD;
             stimulation (voluminous hair and large amount of subcutaneous fat in the arms).&#xD;
&#xD;
          -  Severe heart disease.&#xD;
&#xD;
          -  Allergy to latex and dermatitis.&#xD;
&#xD;
          -  Epileptic seizures or using medications that reduce the threshold for epileptic&#xD;
             seizures.&#xD;
&#xD;
          -  Travel distance to the study site more than 70 Km.&#xD;
&#xD;
          -  Involvement in other clinical treatment trials related to stroke.&#xD;
&#xD;
          -  Participant does not want to be informed about the potential fortuitous discoveries&#xD;
             that may contribute to the prevention, diagnosis and treatment of existing or probable&#xD;
             diseases in the future.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Friedhelm Hummel, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Ecole Politechnique Federale de Lausanne</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Friedhelm Hummel, MD</last_name>
    <phone>+41 21 69 35 440</phone>
    <email>friedhelm.hummel@epfl.ch</email>
  </overall_contact>
  <location>
    <facility>
      <name>Clinique Romande de Readaptation (CRR)</name>
      <address>
        <city>Sion</city>
        <country>Switzerland</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Friedhelm Hummel, MD</last_name>
    </contact>
  </location>
  <location_countries>
    <country>Switzerland</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>June 15, 2020</study_first_submitted>
  <study_first_submitted_qc>June 23, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 26, 2020</study_first_posted>
  <last_update_submitted>January 6, 2023</last_update_submitted>
  <last_update_submitted_qc>January 6, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 9, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Stroke</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT04448483
org study id: AVANCER
nct id: NCT04448483
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This study aims to evaluate safety, tolerability and efficacy of a new treatment for upper
      limb motor rehabilitation after severe stroke using non-invasive neurotechnologies. The
      investigational system is used alone or coupled with brain stimulation provided by
      transcranic direct current stimulation.
This study aims at providing two interventions:

      In the first intervention, a brain computer interface able to non-invasively detect motor
      intention from the non-invasive measure of brain activity by using electroencephalography
      (BrainVision, V-amp) activates a robotic glove (Gloreha Sinfonia, Idrogenet Srl) that will
      assist-as-needed hand movements and paretic upper limb functional electric stimulation
      (RehaStim, Hasomed). The latter will activate upper limb muscles to perform motor
      rehabilitation exercises for the upper limb. The motor rehabilitation exercises include upper
      limb and hand mobilization and functional tasks, such as hand open/closing, wrist
      flexion/extension, and reach and grasp a cup, keep and release.

      In the second intervention, non-invasive brain stimulation (DC-Stimulator, NeuroConn) in the
      form of transcranial direct current stimulation will be provided in addition to the previous
      intervention.

      Each participant will perform a minimum of 11 rehabilitative sessions for the first
      intervention and a minimum of 11 rehabilitative sessions for the second intervention, for a
      total minimum of 22 rehabilitative sessions. If the participant recovers with the
      intervention, the relative rehabilitative session continues to be proposed until patients
      will reaches a "plateau". The intervention will switch from 1 to 2 if the participant does
      not improve anymore with the 1st intervention. If the patient does not improve anymore with
      the 2nd intervention the interventional part of the trial will be finished. The
      intervention(s) will terminate also if the participant continues to progress after 6 months
      of inclusion. As the study is especially designed for personalization of intervention for
      every patient, it is not possible to determine a priori the number of sessions for each
      participant, because they depend on the response of each participant to the intervention. The
      duration of each rehabilitative visit is about two and half hours.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Change in functional improvement of upper limbs along training sessions
time frame: 10 months average
description: Measurement of improvement before and after training of upper limb, using Fugl-Meyer (FMA) scale (0-66).
FMA is a stroke specific index to estimate motor function. Measurements are performed every second training session and at the evaluation visit.
measure: Change in speed and coordination of the affected side
time frame: 10 months average
description: Measurement of speed and coordination of the affected side are performed using FMA modified score, max 54.
Measurements are performed every second training session.
measure: Change in sensorimotor status in the two upper limbs
time frame: 10 months average
description: Measurement of sensorimotor status in the two upper limbs, using Fugl-Meyer (FMA) scale (0-66).
Measurements are performed at the evaluation visit.
measure: Action Reach Arm Test (ARAT)
time frame: 10 months average
description: Upper limb functions changes measured by the ARAT test (ARAT scale: 0-57) in the two upper limbs.
Measurements are performed at the evaluation visit.
measure: Fatigue Visual Analog Scale (VAS)
time frame: 10 months average
description: Measurement of fatigue is made with the Visual Analog Scale (VAS; 0-100). Measurements are performed every second training session.
measure: Rivermead Assessment of Somatosensory Performance (RASP)
time frame: 10 months average
description: Somatosensory function are measured with RASP (RASP; 0-210) in the two upper limbs.
Measurements are performed at the evaluation visit.
measure: Brain stimulation effectiveness in BCI-aided motor therapy
time frame: 10 months average
description: The measurement of the effectiveness of brain stimulation is measured by FMA scores of all patients at initial, inter-intervention and final evaluation. This measurement is made between the end and the beginning of each intervention for each patient.
Comparison is made by using one-way ANOVA if data normally distributed, or Kruskal Wallis test if otherwise. Secondary analysis measures are calculated for each patient once they complete the study. It will consist in the evaluation of effectiveness of BCI-aided motor therapy without and with brain stimulation. Group comparison is done with inferential statistics for full and partial populations. Similar comparisons and judgement criteria are applied for clinical scales and questionnaires.
arm group label: Group A
arm group type: Experimental
description: Patients belonging to group A will start intervention I, immediately after baseline. We will recruit about 25 for group A (randomization will take into account the two to one study design) in order to have about 20 patients in Group A that will complete the study.
arm group label: Group B
arm group type: Experimental
description: Patients belonging to group B will follow an observation period (max. 3 months) before starting intervention I. We will recruit about 15 patients for group B (randomization will take into account the two to one study design) in order to have about 10 patients in Group B that will complete the study.
intervention type: Device
intervention name: Paretic upper limb functional electric stimulation through RehaStim
description: The stimulation will activate upper limb muscles to perform motor rehabilitation exercises for the upper limb with the help of the Gloreha Sinfonia robotic glove that will assist-as-needed hands movements. Motor intention will be detected by a BCI (Brain Computer Interface) from the non-invasive measure of brain activity by using electroencephalography.
The motor rehabilitation exercises include upper limb and hand mobilization and functional tasks, such as hand open/closing, wrist flexion/extension, and reach and grasp a cup, keep and release.
arm group label: Group A
arm group label: Group B
intervention type: Device
intervention name: Non-invasive transcranial current stimulation through DC-Stimulator
description: Non-invasive brain stimulation in the form of transcranial direct current stimulation will be provided in addition to the previous intervention.
arm group label: Group A
arm group label: Group B
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Friedhelm Hummel, MD
role: Principal Investigator
affiliation: Ecole Politechnique Federale de Lausanne
last name: Friedhelm Hummel, MD
phone: +41 21 69 35 440
email: friedhelm.hummel@epfl.ch
facility: 
status: Recruiting
contact: 
country: Switzerland
responsible party type: Sponsor
mesh term: Stroke
sharing ipd: Undecided