<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/NCT02249676</url>
  </required_header>
  <id_info>
    <org_study_id>IRB2013-055-02</org_study_id>
    <nct_id>NCT02249676</nct_id>
  </id_info>
  <brief_title>Autologous Mesenchymal Stem Cells for the Treatment of Neuromyelitis Optica Spectrum Disorders</brief_title>
  <official_title>Autologous Mesenchymal Stem Cells for the Treatment of Progressive and Refractory Neuromyelitis Optica Spectrum Disorders: an Open-label Phase 2a Proof-of-concept Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Tianjin Medical University General Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Tianjin Medical University General Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Neuromyelitis optica (NMO) is a demyelinating and degenerative disorder of the central&#xD;
      nervous system affecting vision and brain and spinal cord function which leads to&#xD;
      accumulating disability with a 5 year-mortality of approximately 30%. Survivors are typically&#xD;
      left with severe morbidity secondary to blindness, quadriparesis and respiratory failure. No&#xD;
      agent has been found to be highly effective in halting disease activity.Based on recent&#xD;
      outcomes of Multipotent mesenchymal stromal cells in autoimmune diseases including multiple&#xD;
      sclerosis, and based on the mechanisms of neuromyelitis optica, the investigators anticipate&#xD;
      that mesenchymal stem cells transplantation may provide lasting disease stability for&#xD;
      neuromyelitis optica patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Primary objective was to assess feasibility and safety; the investigators compared adverse&#xD;
      events from up to 3months before treatment until up to 12 months after the infusion.&#xD;
&#xD;
      As a secondary objective, the investigators chose efficacy outcomes to assess the Expanded&#xD;
      Disability Status (EDSS)、annual relapse rate (ARR) and time to next relapse after transplant.&#xD;
&#xD;
      Third objective anterior visual pathway and pyramidal tract as a model of wider disease.&#xD;
      Masked endpoint analyses was used for electrophysiological and selected imaging outcomes.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 2013</start_date>
  <completion_date type="Actual">December 31, 2014</completion_date>
  <primary_completion_date type="Actual">December 31, 2014</primary_completion_date>
  <phase>Phase 2</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>EDSS</measure>
    <time_frame>change from baseline to one year</time_frame>
    <description>Compare EDSS change before and one year after mesenchymal stem cells (MSC) infusion</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Annual relapse rate</measure>
    <time_frame>1 year after infusion</time_frame>
    <description>Compare annual relapse rate before and one year after MSC infusion</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lesion load</measure>
    <time_frame>1 year after infusion</time_frame>
    <description>Compared lesion load before and one year after MSC infusion</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Retinal nerve fiber layer (RNFL)</measure>
    <time_frame>1 year after infusion</time_frame>
    <description>Compared RNFL before and one year after MSC infusion</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cognition</measure>
    <time_frame>1 year after infusion</time_frame>
    <description>Compare cognition questionnaire scale before and one year after MSC infusion</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immunological assessments</measure>
    <time_frame>1 year after infusion</time_frame>
    <description>Compare anti-aquaporin4-ab before and one year after MSC infusion.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immunological assessments</measure>
    <time_frame>1 year after infusion</time_frame>
    <description>Compare immune cell subpopulation before and one year after MSC infusion.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immunological assessments</measure>
    <time_frame>1 year after infusion</time_frame>
    <description>Compare cytokine kinetics before and one year after MSC infusion.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>cerebral volume</measure>
    <time_frame>1 year after infusion</time_frame>
    <description>Compare cerebral volume before and one year after MSC infusion</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">15</enrollment>
  <condition>Devic's Syndrome</condition>
  <condition>Devic's Neuromyelitis Optica</condition>
  <condition>Devic Syndrome</condition>
  <condition>Devic's Disease</condition>
  <condition>Devic Disease</condition>
  <arm_group>
    <arm_group_label>Autologous mesenchymal stem cells group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Generated clinical-grade MSC 10 mg chlorpheniramine Po.;100 mg hydrocortisone iv.;10 mg metoclopramide im.;30 min before administration of the cells .&#xD;
MSC a day-case 2·0×106 cells/kg i.v. 15min Infused normal saline 500 Ml over 4 h i.v.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Patients with progressive and refractory NMO treated with regular methods</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Autologous mesenchymal stem cells</intervention_name>
    <description>Autologous mesenchymal stem cells</description>
    <arm_group_label>Autologous mesenchymal stem cells group</arm_group_label>
    <arm_group_label>Control group</arm_group_label>
    <other_name>MSC</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Clinically definite neuromyelitis optica or neuromyelitis optica spectrum disorder&#xD;
&#xD;
          -  Age &gt; 18 year&#xD;
&#xD;
          -  EDSS &gt; 3&#xD;
&#xD;
          -  Progression continued relapses or worsening MRI after at least a year of attempted&#xD;
             therapy as evidenced by one or more of the following:&#xD;
&#xD;
               -  Increase of 1 EDSS point (if baseline EDSS&lt;5.0) or 0.5 EDSS points (if baseline&#xD;
                  EDSS &gt;5.5)&#xD;
&#xD;
               -  Moderate-severe relapses in past 18 months&#xD;
&#xD;
               -  Gadolinium enhancing lesions (double or triple dose Gd)&#xD;
&#xD;
               -  1 new T2 lesion&#xD;
&#xD;
          -  Evidence of recent inflammatory disease, as evidenced by any one of the following:&#xD;
&#xD;
               -  1 moderate-severe relapses in past 18 months&#xD;
&#xD;
               -  1 Gd-enhancing lesions (single, double or triple dose Gd)&#xD;
&#xD;
               -  1 new T2 lesion&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Received Immune inhibitors immunomodulator during the three months before the trial&#xD;
&#xD;
          -  Significant cardiac, renal, or hepatic failure or any other disease that may affect&#xD;
             the results of the study&#xD;
&#xD;
          -  Allergies&#xD;
&#xD;
          -  Pregnant or possibly pregnant&#xD;
&#xD;
          -  Cognitive decline to understand or sign the informed consent&#xD;
&#xD;
          -  Brain tumor, HIV (+) tumor marker (+), blood pressure (BP): 200 /110 mmHg&#xD;
&#xD;
          -  Judged not suitable by doctors&#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>Fu-Dong Shi, MD,PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Tianjin Medical University General Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Tianjin Medical University General Hospital</name>
      <address>
        <city>Tianjin</city>
        <state>Tianjin</state>
        <zip>300052</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>October 2018</verification_date>
  <study_first_submitted>September 15, 2014</study_first_submitted>
  <study_first_submitted_qc>September 22, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 25, 2014</study_first_posted>
  <last_update_submitted>October 15, 2018</last_update_submitted>
  <last_update_submitted_qc>October 15, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">October 17, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Tianjin Medical University General Hospital</investigator_affiliation>
    <investigator_full_name>Fu-Dong Shi</investigator_full_name>
    <investigator_title>Head of Neurology Department</investigator_title>
  </responsible_party>
  <keyword>Autologous mesenchymal stem cells</keyword>
  <keyword>neuromyelitis optica</keyword>
  <keyword>treatment</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neuromyelitis Optica</mesh_term>
    <mesh_term>Syndrome</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/NCT02249676
org study id: IRB2013-055-02
nct id: NCT02249676
lead sponsor: 
has dmc: Yes
Neuromyelitis optica (NMO) is a demyelinating and degenerative disorder of the central
      nervous system affecting vision and brain and spinal cord function which leads to
      accumulating disability with a 5 year-mortality of approximately 30%. Survivors are typically
      left with severe morbidity secondary to blindness, quadriparesis and respiratory failure. No
      agent has been found to be highly effective in halting disease activity.Based on recent
      outcomes of Multipotent mesenchymal stromal cells in autoimmune diseases including multiple
      sclerosis, and based on the mechanisms of neuromyelitis optica, the investigators anticipate
      that mesenchymal stem cells transplantation may provide lasting disease stability for
      neuromyelitis optica patients.
Primary objective was to assess feasibility and safety; the investigators compared adverse
      events from up to 3months before treatment until up to 12 months after the infusion.

      As a secondary objective, the investigators chose efficacy outcomes to assess the Expanded
      Disability Status (EDSS)、annual relapse rate (ARR) and time to next relapse after transplant.

      Third objective anterior visual pathway and pyramidal tract as a model of wider disease.
      Masked endpoint analyses was used for electrophysiological and selected imaging outcomes.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: EDSS
time frame: change from baseline to one year
description: Compare EDSS change before and one year after mesenchymal stem cells (MSC) infusion
measure: Annual relapse rate
time frame: 1 year after infusion
description: Compare annual relapse rate before and one year after MSC infusion
measure: Lesion load
time frame: 1 year after infusion
description: Compared lesion load before and one year after MSC infusion
measure: Retinal nerve fiber layer (RNFL)
time frame: 1 year after infusion
description: Compared RNFL before and one year after MSC infusion
measure: Cognition
time frame: 1 year after infusion
description: Compare cognition questionnaire scale before and one year after MSC infusion
measure: Immunological assessments
time frame: 1 year after infusion
description: Compare anti-aquaporin4-ab before and one year after MSC infusion.
measure: Immunological assessments
time frame: 1 year after infusion
description: Compare immune cell subpopulation before and one year after MSC infusion.
measure: Immunological assessments
time frame: 1 year after infusion
description: Compare cytokine kinetics before and one year after MSC infusion.
measure: cerebral volume
time frame: 1 year after infusion
description: Compare cerebral volume before and one year after MSC infusion
arm group label: Autologous mesenchymal stem cells group
arm group type: Experimental
description: Generated clinical-grade MSC 10 mg chlorpheniramine Po.;100 mg hydrocortisone iv.;10 mg metoclopramide im.;30 min before administration of the cells .
MSC a day-case 2·0×106 cells/kg i.v. 15min Infused normal saline 500 Ml over 4 h i.v.
arm group label: Control group
arm group type: Placebo Comparator
description: Patients with progressive and refractory NMO treated with regular methods
intervention type: Biological
intervention name: Autologous mesenchymal stem cells
description: Autologous mesenchymal stem cells
arm group label: Autologous mesenchymal stem cells group
arm group label: Control group
other name: MSC
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Fu-Dong Shi, MD,PhD
role: Principal Investigator
affiliation: Tianjin Medical University General Hospital
facility: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Tianjin Medical University General Hospital
investigator full name: Fu-Dong Shi
investigator title: Head of Neurology Department
mesh term: Neuromyelitis Optica
mesh term: Syndrome