<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/NCT04488965</url>
  </required_header>
  <id_info>
    <org_study_id>AVCell2020</org_study_id>
    <nct_id>NCT04488965</nct_id>
  </id_info>
  <brief_title>Study of the Therapeutic Effects of Cortical Autograft Implantation in Patients With Cerebral Ischemia</brief_title>
  <acronym>AVCell</acronym>
  <official_title>Study of the Therapeutic Effects of Cortical Autograft Implantation in Patients With Cerebral Ischemia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Centre Hospitalier Universitaire Vaudois</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Centre Hospitalier Universitaire Vaudois</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>
      Brain lesions in the adult have dramatic consequences, because the spontaneous capacity of&#xD;
      the brain to functionally recover is limited. Besides existing rehabilitative therapeutic&#xD;
      approaches (e.g. physiotherapy), several lines of research aim at developing treatments to&#xD;
      promote and refine brain plasticity to enhance functional recovery following brain injury.&#xD;
&#xD;
      This pilot clinical study aims at enrolling subjects victim of a stroke with neuronal&#xD;
      destruction leading to a disabling motor deficit. Usually these patients benefit from&#xD;
      intensive neurorehabilitation which allows them to progress up to a certain point but when&#xD;
      their recovery plateau is reached; current medicine is disarmed and no effective treatment&#xD;
      allows, to date, to improve further their performance. This monocentric pilot study aims at&#xD;
      evaluating the feasibility and safety of Autologous Neural Cell Ecosystems (ANCE), which is a&#xD;
      cortical autograft intended to be used on stroke patients, for the replacement of motor&#xD;
      neurons destroyed during an ischemic stroke.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Using neural grafts to restore function after lesions of the central nervous system is a&#xD;
      challenging strategy. Most of the transplantation experience acquired the last decades was&#xD;
      focused on fetal neuronal grafts. However, despite the great enthusiasm generated by this&#xD;
      approach, ethical controversies, immune rejection, and lack of fetal donors remain a major&#xD;
      problem. Therefore, autotransplantation of adult brain cells represents an attractive&#xD;
      restoration alternative to bypass the caveats of fetal grafting.&#xD;
&#xD;
      The optimization of the procedure to obtain ANCE, a cortical autograft obtained from cortical&#xD;
      biopsy, was first successfully demonstrated in producing long-term primary culture of adult&#xD;
      human brain cells from temporal lobe tissues obtained from epilepsy and trauma neurosurgical&#xD;
      patients. ANCE has been characterized as an ecosystem of autologous neural cells in&#xD;
      suspension, composed of several cell types: astrocytes, proliferative progenitors and&#xD;
      quiescent progenitors.&#xD;
&#xD;
      The production of ANCE has been implemented to prepare long-term primary culture from primate&#xD;
      cortical biopsies. This allowed assessing the feasibility of autotransplantation from brain&#xD;
      biopsy to reimplantation of cultured brain cells in a non-human primate model of motor cortex&#xD;
      lesion. On the same model of cerebral cortex lesion in nonhuman primates, further study&#xD;
      demonstrated, by quantitative behavioral evidence, the beneficial outcome of cell therapy&#xD;
      following injury of the cerebral cortex.&#xD;
&#xD;
      Based on the encouraging results from past experiences on non-human primate model of motor&#xD;
      cortex lesion, this monocentric pilot study aims at evaluating the feasibility and safety of&#xD;
      ANCE (Autologous Neural Cell Ecosystems), which is cortical autograft intended to be used on&#xD;
      stroke patients, for the replacement of motor neurons destroyed during an ischemic stroke.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Not yet recruiting</overall_status>
  <start_date type="Anticipated">December 1, 2020</start_date>
  <completion_date type="Anticipated">September 1, 2025</completion_date>
  <primary_completion_date type="Anticipated">September 1, 2025</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>monocentric, non-randomized, open-label with single-arm design</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Assess the feasibility and safety of ANCE treatment by evaluating the incidence of treatment-related adverse events</measure>
    <time_frame>54 months (Visits will be carried out 2 years and 4 years after reimplantation in order to ensure that there is no long-term complication of ANCE reimplantation)</time_frame>
    <description>Successful collection of the cortical biopsy; in vitro production of the cortical autograft from the cortical biopsy; and reimplantation of the transplant without treatment-related serious adverse events.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in the medium term of the participant score when assessing the &quot;Catherine Bergego Scale&quot; (CBS)</measure>
    <time_frame>up to 54 months (Assessment is performed at each visit up to the last visit 4 years after reimplantation)</time_frame>
    <description>CBS is an observational, functional, performance based assessment, being 0 (indicating no neglect) to 30 (indicating severe neglect).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in the medium term of the participant score when assessing the NIHSS</measure>
    <time_frame>up to 54 months (Assessment is performed at each visit up to the last visit 4 years after reimplantation)</time_frame>
    <description>NIHSS quantifies the impairment caused by a stroke, being 0 no stroke symptoms, and 42 severe impairment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in the medium term of the participant score when assessing the Modified Rankin Scale</measure>
    <time_frame>up to 54 months (Assessment is performed at each visit up to the last visit 4 years after reimplantation)</time_frame>
    <description>The Modified Rankin Scale measures the degree of disability or dependence in the daily activities, being 0 no symptoms, 5 severe disability and 6 dead.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in the medium term of the patient score when assessing the Action Research Arm Test (ARAT)</measure>
    <time_frame>up to 54 months (Assessment is performed at each visit up to the last visit 4 years after reimplantation)</time_frame>
    <description>ARAT assesses upper limb functioning using observational methods (19 item measure divided into 4 sub-tests (grasp, grip, pinch, and gross arm movement)), being 0 incapability to perform the test, and 57 being able to perform the test normally.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in the medium term of the patient score when assessing the Box and Block Test (BBT)</measure>
    <time_frame>up to 54 months (Assessment is performed at each visit up to the last visit 4 years after reimplantation)</time_frame>
    <description>BBT measures unilateral gross manual dexterity. The BBT is composed of a box divided in two compartments by a partition and 150 blocks. Participants are scored based on the number of blocks transferred from one compartment to the other compartment in 60 seconds. Higher scores are indicative of better manual dexterity.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in the medium term of the patient score when assessing the Resistance to passive movement scale (Repas)</measure>
    <time_frame>up to 54 months (Assessment is performed at each visit up to the last visit 4 years after reimplantation)</time_frame>
    <description>Assessed for the upper limb and lower limb (maximum score being 56 and 48, respectively, being 0 no increase in muscle tone and the maximum score increased resistance to passive movement (affected part rigid in flexion or extension).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in the medium term of the patient score when assessing Activities of Daily Living (ADL)</measure>
    <time_frame>up to 54 months (Assessment is performed at each visit up to the last visit 4 years after reimplantation)</time_frame>
    <description>Activities of Daily Living (ADLs) are tasks related to personal care: for each task the score varies from 7 when completely independent, to 1 when requiring total support. Hence, higher scores are indicative of better functional independence.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in the medium term of the patient score when assessing Rivermead Mobility Index</measure>
    <time_frame>up to 54 months (Assessment is performed at each visit up to the last visit 4 years after reimplantation)</time_frame>
    <description>The Rivermead Mobility Index is a measure of disability related to bodily mobility. It demonstrates the patient's ability to move her or his own body, being 0 the lowest score and 15 the highest. The highest the score the better the mobility.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in the medium term of the patient score when assessing Berg Balance Scale</measure>
    <time_frame>up to 54 months (Assessment is performed at each visit up to the last visit 4 years after reimplantation)</time_frame>
    <description>The Berg balance scale is used to objectively determine a patient's ability (or inability) to safely balance during a series of 14 predetermined tasks. Score ranges from 0 to 4 for each task, being the highest total score 56, i.e. completely independent.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in the medium term of the patient score when assessing London Handicap Scale (LHS)</measure>
    <time_frame>up to 54 months (Assessment is performed at each visit up to the last visit 4 years after reimplantation)</time_frame>
    <description>The London Handicap Scale can be used to determine the effect of chronic disorders on a person's functional ability using a self-completion questionnaire. Minimum scale value is 0 and maximum is 1, with 1 indicating normal function.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">10</enrollment>
  <condition>Ischemic Stroke</condition>
  <arm_group>
    <arm_group_label>Autologous neural cell ecosystems - ANCE</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The patient will undergo first surgery under general anesthesia for the collection of the cortical biopsy (5x5x5 mm biopsy of non-dominant frontal cortex). After the production of ANCE from the cortical biopsy, which last 8 to 12 weeks, the patient will undergo a second neurosurgery, for the stereotaxic reimplantation of ANCE under general anesthesia.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Autologous transplant</intervention_name>
    <description>Autologous transplant obtained from cortical biopsy</description>
    <arm_group_label>Autologous neural cell ecosystems - ANCE</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Be between 18 and 75 years old.&#xD;
&#xD;
          -  Victim of a first ischemic stroke in superficial Sylvian territory with at least&#xD;
             frontal damage.&#xD;
&#xD;
          -  Cerebral ischemic lesion demonstrated by MRI.&#xD;
&#xD;
          -  Stroke older than one year.&#xD;
&#xD;
          -  Presence of a motor hemi-syndrome with at least one involvement of the upper limb.&#xD;
&#xD;
          -  Stable neurological deficit in motor function of the limb greater than two months&#xD;
             apart before enrolling the patient in the study.&#xD;
&#xD;
          -  Woman of childbearing potential with a negative blood pregnancy test before the biopsy&#xD;
             and using a reliable method of contraception during the study.&#xD;
&#xD;
          -  Patient capable of discernment and of giving informed consent himself.&#xD;
&#xD;
          -  Absence of other serious pathologies or comorbidities.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Brain lesions or a history of stroke or brain hemorrhage.&#xD;
&#xD;
          -  Signs of peripheral neurological damage, such as radicular or trunk involvement&#xD;
&#xD;
          -  History of spinal cord problems.&#xD;
&#xD;
          -  History of neurosurgical intervention in the brain.&#xD;
&#xD;
          -  surgical intervention contraindications.&#xD;
&#xD;
          -  Anticoagulation, if it cannot be interrupted one week before and one week after each&#xD;
             of the 2 brain surgeries.&#xD;
&#xD;
          -  Coagulation disorders.&#xD;
&#xD;
          -  Treatment of botulinum toxin during the last 3 months before inclusion.&#xD;
&#xD;
          -  Seizures or anti-epileptic treatment.&#xD;
&#xD;
          -  Global cognitive disorders, such as degenerative or vascular dementia.&#xD;
&#xD;
          -  High blood pressure difficult to control.&#xD;
&#xD;
          -  Alcohol or drug abuse.&#xD;
&#xD;
          -  Known neoplasia.&#xD;
&#xD;
          -  Inability to understand or cooperate in the study.&#xD;
&#xD;
          -  MRI contraindication&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Penicillin intolerance or allergy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Jocelyne Bloch, Pr MD</last_name>
    <phone>+41795562951</phone>
    <email>jocelyne.bloch@chuv.ch</email>
  </overall_contact>
  <location>
    <facility>
      <name>Centre Hospitalier Universitaire Vaudois</name>
      <address>
        <city>Lausanne</city>
        <state>Canton De Vaud</state>
        <zip>1011</zip>
        <country>Switzerland</country>
      </address>
    </facility>
    <contact>
      <last_name>Jocelyne Bloch, MD</last_name>
      <phone>+41 21 314 12 93</phone>
      <email>jocelyne.bloch@chuv.ch</email>
    </contact>
  </location>
  <location_countries>
    <country>Switzerland</country>
  </location_countries>
  <verification_date>November 2020</verification_date>
  <study_first_submitted>June 2, 2020</study_first_submitted>
  <study_first_submitted_qc>July 23, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 28, 2020</study_first_posted>
  <last_update_submitted>November 2, 2020</last_update_submitted>
  <last_update_submitted_qc>November 2, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">November 3, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Centre Hospitalier Universitaire Vaudois</investigator_affiliation>
    <investigator_full_name>Jocelyne Bloch</investigator_full_name>
    <investigator_title>Associate professor</investigator_title>
  </responsible_party>
  <keyword>autologous transplant</keyword>
  <keyword>brain cell therapy</keyword>
  <keyword>motor cortex lesion</keyword>
  <keyword>cortical autograft</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ischemic Stroke</mesh_term>
    <mesh_term>Brain Ischemia</mesh_term>
    <mesh_term>Cerebral Infarction</mesh_term>
    <mesh_term>Ischemia</mesh_term>
  </condition_browse>
  <!-- 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/NCT04488965
org study id: AVCell2020
nct id: NCT04488965
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Brain lesions in the adult have dramatic consequences, because the spontaneous capacity of
      the brain to functionally recover is limited. Besides existing rehabilitative therapeutic
      approaches (e.g. physiotherapy), several lines of research aim at developing treatments to
      promote and refine brain plasticity to enhance functional recovery following brain injury.

      This pilot clinical study aims at enrolling subjects victim of a stroke with neuronal
      destruction leading to a disabling motor deficit. Usually these patients benefit from
      intensive neurorehabilitation which allows them to progress up to a certain point but when
      their recovery plateau is reached; current medicine is disarmed and no effective treatment
      allows, to date, to improve further their performance. This monocentric pilot study aims at
      evaluating the feasibility and safety of Autologous Neural Cell Ecosystems (ANCE), which is a
      cortical autograft intended to be used on stroke patients, for the replacement of motor
      neurons destroyed during an ischemic stroke.
Using neural grafts to restore function after lesions of the central nervous system is a
      challenging strategy. Most of the transplantation experience acquired the last decades was
      focused on fetal neuronal grafts. However, despite the great enthusiasm generated by this
      approach, ethical controversies, immune rejection, and lack of fetal donors remain a major
      problem. Therefore, autotransplantation of adult brain cells represents an attractive
      restoration alternative to bypass the caveats of fetal grafting.

      The optimization of the procedure to obtain ANCE, a cortical autograft obtained from cortical
      biopsy, was first successfully demonstrated in producing long-term primary culture of adult
      human brain cells from temporal lobe tissues obtained from epilepsy and trauma neurosurgical
      patients. ANCE has been characterized as an ecosystem of autologous neural cells in
      suspension, composed of several cell types: astrocytes, proliferative progenitors and
      quiescent progenitors.

      The production of ANCE has been implemented to prepare long-term primary culture from primate
      cortical biopsies. This allowed assessing the feasibility of autotransplantation from brain
      biopsy to reimplantation of cultured brain cells in a non-human primate model of motor cortex
      lesion. On the same model of cerebral cortex lesion in nonhuman primates, further study
      demonstrated, by quantitative behavioral evidence, the beneficial outcome of cell therapy
      following injury of the cerebral cortex.

      Based on the encouraging results from past experiences on non-human primate model of motor
      cortex lesion, this monocentric pilot study aims at evaluating the feasibility and safety of
      ANCE (Autologous Neural Cell Ecosystems), which is cortical autograft intended to be used on
      stroke patients, for the replacement of motor neurons destroyed during an ischemic stroke.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: monocentric, non-randomized, open-label with single-arm design
primary purpose: Treatment
masking: None (Open Label)
measure: Assess the feasibility and safety of ANCE treatment by evaluating the incidence of treatment-related adverse events
time frame: 54 months (Visits will be carried out 2 years and 4 years after reimplantation in order to ensure that there is no long-term complication of ANCE reimplantation)
description: Successful collection of the cortical biopsy; in vitro production of the cortical autograft from the cortical biopsy; and reimplantation of the transplant without treatment-related serious adverse events.
measure: Change in the medium term of the participant score when assessing the "Catherine Bergego Scale" (CBS)
time frame: up to 54 months (Assessment is performed at each visit up to the last visit 4 years after reimplantation)
description: CBS is an observational, functional, performance based assessment, being 0 (indicating no neglect) to 30 (indicating severe neglect).
measure: Change in the medium term of the participant score when assessing the NIHSS
time frame: up to 54 months (Assessment is performed at each visit up to the last visit 4 years after reimplantation)
description: NIHSS quantifies the impairment caused by a stroke, being 0 no stroke symptoms, and 42 severe impairment.
measure: Change in the medium term of the participant score when assessing the Modified Rankin Scale
time frame: up to 54 months (Assessment is performed at each visit up to the last visit 4 years after reimplantation)
description: The Modified Rankin Scale measures the degree of disability or dependence in the daily activities, being 0 no symptoms, 5 severe disability and 6 dead.
measure: Change in the medium term of the patient score when assessing the Action Research Arm Test (ARAT)
time frame: up to 54 months (Assessment is performed at each visit up to the last visit 4 years after reimplantation)
description: ARAT assesses upper limb functioning using observational methods (19 item measure divided into 4 sub-tests (grasp, grip, pinch, and gross arm movement)), being 0 incapability to perform the test, and 57 being able to perform the test normally.
measure: Change in the medium term of the patient score when assessing the Box and Block Test (BBT)
time frame: up to 54 months (Assessment is performed at each visit up to the last visit 4 years after reimplantation)
description: BBT measures unilateral gross manual dexterity. The BBT is composed of a box divided in two compartments by a partition and 150 blocks. Participants are scored based on the number of blocks transferred from one compartment to the other compartment in 60 seconds. Higher scores are indicative of better manual dexterity.
measure: Change in the medium term of the patient score when assessing the Resistance to passive movement scale (Repas)
time frame: up to 54 months (Assessment is performed at each visit up to the last visit 4 years after reimplantation)
description: Assessed for the upper limb and lower limb (maximum score being 56 and 48, respectively, being 0 no increase in muscle tone and the maximum score increased resistance to passive movement (affected part rigid in flexion or extension).
measure: Change in the medium term of the patient score when assessing Activities of Daily Living (ADL)
time frame: up to 54 months (Assessment is performed at each visit up to the last visit 4 years after reimplantation)
description: Activities of Daily Living (ADLs) are tasks related to personal care: for each task the score varies from 7 when completely independent, to 1 when requiring total support. Hence, higher scores are indicative of better functional independence.
measure: Change in the medium term of the patient score when assessing Rivermead Mobility Index
time frame: up to 54 months (Assessment is performed at each visit up to the last visit 4 years after reimplantation)
description: The Rivermead Mobility Index is a measure of disability related to bodily mobility. It demonstrates the patient's ability to move her or his own body, being 0 the lowest score and 15 the highest. The highest the score the better the mobility.
measure: Change in the medium term of the patient score when assessing Berg Balance Scale
time frame: up to 54 months (Assessment is performed at each visit up to the last visit 4 years after reimplantation)
description: The Berg balance scale is used to objectively determine a patient's ability (or inability) to safely balance during a series of 14 predetermined tasks. Score ranges from 0 to 4 for each task, being the highest total score 56, i.e. completely independent.
measure: Change in the medium term of the patient score when assessing London Handicap Scale (LHS)
time frame: up to 54 months (Assessment is performed at each visit up to the last visit 4 years after reimplantation)
description: The London Handicap Scale can be used to determine the effect of chronic disorders on a person's functional ability using a self-completion questionnaire. Minimum scale value is 0 and maximum is 1, with 1 indicating normal function.
arm group label: Autologous neural cell ecosystems - ANCE
arm group type: Experimental
description: The patient will undergo first surgery under general anesthesia for the collection of the cortical biopsy (5x5x5 mm biopsy of non-dominant frontal cortex). After the production of ANCE from the cortical biopsy, which last 8 to 12 weeks, the patient will undergo a second neurosurgery, for the stereotaxic reimplantation of ANCE under general anesthesia.
intervention type: Other
intervention name: Autologous transplant
description: Autologous transplant obtained from cortical biopsy
arm group label: Autologous neural cell ecosystems - ANCE
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Jocelyne Bloch, Pr MD
phone: +41795562951
email: jocelyne.bloch@chuv.ch
facility: 
contact: 
country: Switzerland
responsible party type: Principal Investigator
investigator affiliation: Centre Hospitalier Universitaire Vaudois
investigator full name: Jocelyne Bloch
investigator title: Associate professor
mesh term: Ischemic Stroke
mesh term: Brain Ischemia
mesh term: Cerebral Infarction
mesh term: Ischemia