<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/NCT01716481</url>
  </required_header>
  <id_info>
    <org_study_id>2011-10-047</org_study_id>
    <nct_id>NCT01716481</nct_id>
  </id_info>
  <brief_title>The STem Cell Application Researches and Trials In NeuroloGy-2 (STARTING-2) Study</brief_title>
  <acronym>STARTING-2</acronym>
  <official_title>Intravenous Administration of Autoserum-cultured Autologous Mesenchymal Stem Cells in Ischemic Stroke: A Single Center, Randomized, Open Label, Prospective, Phase 3 Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Samsung Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Pharmicell Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Samsung Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The objectives of this study was to test hypothesis that ischemic stroke patients having&#xD;
      moderate to severe persistent neurologic deficit will have better outcomes with intravenous&#xD;
      transplantation of autologous mesenchymal stem cells (MSCs) expanded with autologous serum&#xD;
      that is obtained at acute phase of stroke than patients receiving standard treatment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In this study, we will use autologous 'ischemic' serum that obtained at the earliest time&#xD;
      point as possible (immediate after randomization) for the purpose of ischemic&#xD;
      preconditioning. We have recently conducted preclinical studies on the effects of ischemic&#xD;
      preconditioning on the MSC functions. We have evaluated the characteristics of rat MSCs after&#xD;
      culture with fetal bovine serum (FBS) or serum obtained from rat stroke model. Compared to&#xD;
      FBS, the use of serum obtained from rat stroke model resulted in more rapid expansion of&#xD;
      MSCs, which reduces cell preparation time by increase in G2/M phase, decreased cell&#xD;
      death/senescence, increased trophic factor secretion, and increased migration capacity.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>November 2012</start_date>
  <completion_date type="Anticipated">December 2017</completion_date>
  <primary_completion_date type="Anticipated">December 2017</primary_completion_date>
  <phase>Phase 3</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>Categorical shift in modified Rankin scale (mRS)</measure>
    <time_frame>90 days after the cell treatment</time_frame>
    <description>Categorical shift in mRS at 90 days after the cell treatment</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change of National Institutes of Health stroke scale (NIHSS)</measure>
    <time_frame>90 days after the cell treatment</time_frame>
    <description>Change of NIHSS between pre- and post-treatment 90 days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Early improvement of National Institutes of Health stroke scale (NIHSS)</measure>
    <time_frame>14 days after the cell treatment</time_frame>
    <description>≥5 points improvement or score of 0-2 on NIHSS score at 14 days after treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dichotomized modified Rankin scale (mRS)</measure>
    <time_frame>90 days after the cell treatment</time_frame>
    <description>mRS ≤2 at 90 days after treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of modified Rankin scale (mRS)</measure>
    <time_frame>90 days after the cell treatment</time_frame>
    <description>Change of mRS between pre- and post-treatment 90 days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dichotomized modified Barthel index (mBI)</measure>
    <time_frame>90 days after the cell treatment</time_frame>
    <description>mBI ≥60 at 90 days after treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of modified Barthel index (mBI)</measure>
    <time_frame>90 days after the cell treatment</time_frame>
    <description>Change of mBI between pre- and post-treatment 90 days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of gross motor function</measure>
    <time_frame>90 days after the cell treatment</time_frame>
    <description>Change of Gross motor function (Motricity index and Fugl-Meyer assessment)between pre- and post-treatment 90 days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of Fine motor function</measure>
    <time_frame>90 days after the cell treatment</time_frame>
    <description>Change of Fine motor function (Purdue Pegboard test and Box and block test) between pre- and post-treatment 90 days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of Mobility</measure>
    <time_frame>90 days after the cell treatment</time_frame>
    <description>Change of Mobility (Functional ambulatory category and 10m-Gait speed) between pre- and post-treatment 90 days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of mini-mental status exam (MMSE)</measure>
    <time_frame>90 days after the cell treatment</time_frame>
    <description>Change of MMSE between pre- and post-treatment 90 days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of quality of life</measure>
    <time_frame>90 days after the cell treatment</time_frame>
    <description>Change of EuroQol 5d (EQ-5D) between pre- and post-treatment 90 days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety outcome</measure>
    <time_frame>During 90 days after the cell treatment</time_frame>
    <description>Death: All causes of death&#xD;
Recurrence: Recurrent stroke or transient ischemic attack&#xD;
The immediate reaction:&#xD;
Allergic reactions (tachycardia, fever, skin eruption, leukocytosis) Local complications (hematoma or local infection at the site of bone marrow aspiration) Vascular obstruction (tachypnea, oliguria, or peripheral vascular insufficiency) Systemic complications (infections,laboratory findings).&#xD;
Long-term adverse effects possibly related to MSC treatment Tumor formation (physical examination, plain x-ray, f/u MRI at 90 days after treatment), Aberrant connections (newly diagnosed seizure or arrhythmia)</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Exploration of biomarkers</measure>
    <time_frame>During 90 days after the cell treatment</time_frame>
    <description>SDF(stromal cell-derived factor)-1ɑ (chemokine) S100ß (protection and regeneration) HIF(Hypoxia-inducible factor)-1 (preconditioning) Circulating MSCs and MSC-derived microparticles (CD105-CXCR4(C-X-C chemokine receptor type 4)-PS(phosphoserine)) BDNF (Brain-derived neurotrophic factor) levels and it's polymorphism, and VEGF (Vascular endothelial growth factor) levels&#xD;
Resting-state functional MRI &amp; Diffusion tensor imaging</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Stroke, Ischemic</condition>
  <arm_group>
    <arm_group_label>Mesenchymal stem cell treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard treatment</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Mesenchymal stem cell</intervention_name>
    <description>intravenous transplantation of autologous mesenchymal stem cells expanded with autologous serum</description>
    <arm_group_label>Mesenchymal stem cell treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Men or women (women must be of non-child bearing potential), age 30-75 yrs.&#xD;
&#xD;
          2. Have a stroke that is observed within 90 days of the onset of symptoms&#xD;
&#xD;
          3. Radiologically&#xD;
&#xD;
               1. Relevant lesions within the middle cerebral artery territory (MCA) as assessed&#xD;
                  using diffusion-weighted imaging (DWI).&#xD;
&#xD;
               2. The maximum diameter of the stroke region in any dimension must be ≥15 mm.&#xD;
&#xD;
               3. Not involving more than a half of the ipsilateral periventricular zone&#xD;
&#xD;
          4. Clinically (National Institutes of Health stroke scale, NIHSS)&#xD;
&#xD;
               1. Moderate-to severe persistent neurologic deficit (NIHSS of 6-21 inclusive)&#xD;
&#xD;
               2. New onset of extremity paresis on the affected side, defined as a score of 2-4 on&#xD;
                  the NIHSS Motor Arm (item 5) or Leg (item 6) question.&#xD;
&#xD;
               3. Must be alert or drowsy but easily arousable as defined by score of 0-1 on the&#xD;
                  NIHSS Level of Consciousness question (item 1).&#xD;
&#xD;
               4. &quot;Slow recovery&quot; defined as Change in NIHSS ≤1 point/3 days&#xD;
&#xD;
          5. Willingness&#xD;
&#xD;
               1. Reasonable likelihood of receiving standard physical, occupational and speech&#xD;
                  rehabilitation therapy as indicated for the post stroke deficits.&#xD;
&#xD;
               2. Able to participate in the evaluation process to the point of accurate&#xD;
                  assessment.&#xD;
&#xD;
               3. Willing and able to comply with scheduled visits, lifestyle guidelines, treatment&#xD;
                  plan, laboratory tests, and other study procedures.&#xD;
&#xD;
               4. Evidence of a personally signed and dated informed consent document.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Presence of significant disability prior to the current stroke. Significant disability&#xD;
             is defined as having a pre-stroke modified Rankin score of 2 or more.&#xD;
&#xD;
          2. Have a stroke that is either&#xD;
&#xD;
               1. lacunar infarction&#xD;
&#xD;
               2. Hematologic cause of stroke&#xD;
&#xD;
               3. Recurrent or progressive stroke within 1 week at the time of screening.&#xD;
&#xD;
          3. Hematologic disorders or bone marrow suppression.&#xD;
&#xD;
          4. Have a severe medical illness&#xD;
&#xD;
               1. Severe heart failure&#xD;
&#xD;
               2. Severe febrile illness&#xD;
&#xD;
               3. Hepatic or renal dysfunction&#xD;
&#xD;
               4. Active cancer&#xD;
&#xD;
               5. Any evidence of chronic co-morbid condition or unstable acute systemic illnesses&#xD;
                  which, in the opinion of the investigator, could shorten the subject's survival&#xD;
                  or limit ability to complete the study.&#xD;
&#xD;
          5. Presence of human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C&#xD;
             virus (HCV), or syphilis on admission blood tests&#xD;
&#xD;
          6. Presence of depression that is active and not adequately controlled such that it&#xD;
             interfere with major activities of daily living immediately prior to the current&#xD;
             stroke.&#xD;
&#xD;
          7. Presence of dementia prior to the current stroke that is likely to confound clinical&#xD;
             evaluation.&#xD;
&#xD;
          8. Pregnant females as determined by positive urine human chorionic gonadotropin (hCG)&#xD;
             test or lactating females.&#xD;
&#xD;
          9. Subjects considered unwilling or unable to comply with the procedures and study visit&#xD;
             schedule outlined in the protocol&#xD;
&#xD;
         10. Subjects unwilling to undergo bone marrow aspiration&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Oh Young Bang, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Samsung Medical Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Oh Young Bang, MD</last_name>
    <phone>82-10-3410-3599</phone>
    <email>nmboy@unitel.co.kr</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Sang Ae Park, RN</last_name>
    <phone>82-10-3410-0934</phone>
    <email>sa0124.park@samsung.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Samsung Medical Center, Sungkyunkwan University School of Medicine</name>
      <address>
        <city>Seoul</city>
        <zip>135710</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Suk Jae Kim, MD</last_name>
      <phone>82-2-3410-1895</phone>
      <email>sukjae.kim@gmail.com</email>
    </contact>
    <investigator>
      <last_name>Oh Young Bang, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Suk Jae Kim, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Gyeong Joon Moon, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Yun-Hee Kim, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Sookyoung Ryoo, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Yeon Hee Cho, MS</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Yoon Mi Kang, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Yong Man Kim, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Hyun Soo Kim, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Jun Ho Jang, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Won Hyuk Chang, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Dong Hee Kim, BA</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Ji-Yoon Nam, BA</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Ji Hyun Lee, BA</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Gyeong-Moon Kim, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Chin-Sang Chung, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Kwang Ho Lee, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <verification_date>April 2017</verification_date>
  <study_first_submitted>October 25, 2012</study_first_submitted>
  <study_first_submitted_qc>October 25, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 29, 2012</study_first_posted>
  <last_update_submitted>April 24, 2017</last_update_submitted>
  <last_update_submitted_qc>April 24, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">April 26, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Samsung Medical Center</investigator_affiliation>
    <investigator_full_name>Oh Young Bang</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <keyword>Stroke</keyword>
  <keyword>Mesenchymal stem cells</keyword>
  <keyword>Stem cells</keyword>
  <keyword>Neurogenesis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Stroke</mesh_term>
    <mesh_term>Ischemic Stroke</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/NCT01716481
org study id: 2011-10-047
nct id: NCT01716481
lead sponsor: 
collaborator: 
has dmc: Yes
The objectives of this study was to test hypothesis that ischemic stroke patients having
      moderate to severe persistent neurologic deficit will have better outcomes with intravenous
      transplantation of autologous mesenchymal stem cells (MSCs) expanded with autologous serum
      that is obtained at acute phase of stroke than patients receiving standard treatment.
In this study, we will use autologous 'ischemic' serum that obtained at the earliest time
      point as possible (immediate after randomization) for the purpose of ischemic
      preconditioning. We have recently conducted preclinical studies on the effects of ischemic
      preconditioning on the MSC functions. We have evaluated the characteristics of rat MSCs after
      culture with fetal bovine serum (FBS) or serum obtained from rat stroke model. Compared to
      FBS, the use of serum obtained from rat stroke model resulted in more rapid expansion of
      MSCs, which reduces cell preparation time by increase in G2/M phase, decreased cell
      death/senescence, increased trophic factor secretion, and increased migration capacity.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Categorical shift in modified Rankin scale (mRS)
time frame: 90 days after the cell treatment
description: Categorical shift in mRS at 90 days after the cell treatment
measure: Change of National Institutes of Health stroke scale (NIHSS)
time frame: 90 days after the cell treatment
description: Change of NIHSS between pre- and post-treatment 90 days
measure: Early improvement of National Institutes of Health stroke scale (NIHSS)
time frame: 14 days after the cell treatment
description: ≥5 points improvement or score of 0-2 on NIHSS score at 14 days after treatment
measure: Dichotomized modified Rankin scale (mRS)
time frame: 90 days after the cell treatment
description: mRS ≤2 at 90 days after treatment
measure: Change of modified Rankin scale (mRS)
time frame: 90 days after the cell treatment
description: Change of mRS between pre- and post-treatment 90 days
measure: Dichotomized modified Barthel index (mBI)
time frame: 90 days after the cell treatment
description: mBI ≥60 at 90 days after treatment
measure: Change of modified Barthel index (mBI)
time frame: 90 days after the cell treatment
description: Change of mBI between pre- and post-treatment 90 days
measure: Change of gross motor function
time frame: 90 days after the cell treatment
description: Change of Gross motor function (Motricity index and Fugl-Meyer assessment)between pre- and post-treatment 90 days
measure: Change of Fine motor function
time frame: 90 days after the cell treatment
description: Change of Fine motor function (Purdue Pegboard test and Box and block test) between pre- and post-treatment 90 days
measure: Change of Mobility
time frame: 90 days after the cell treatment
description: Change of Mobility (Functional ambulatory category and 10m-Gait speed) between pre- and post-treatment 90 days
measure: Change of mini-mental status exam (MMSE)
time frame: 90 days after the cell treatment
description: Change of MMSE between pre- and post-treatment 90 days
measure: Change of quality of life
time frame: 90 days after the cell treatment
description: Change of EuroQol 5d (EQ-5D) between pre- and post-treatment 90 days
measure: Safety outcome
time frame: During 90 days after the cell treatment
description: Death: All causes of death
Recurrence: Recurrent stroke or transient ischemic attack
The immediate reaction:
Allergic reactions (tachycardia, fever, skin eruption, leukocytosis) Local complications (hematoma or local infection at the site of bone marrow aspiration) Vascular obstruction (tachypnea, oliguria, or peripheral vascular insufficiency) Systemic complications (infections,laboratory findings).
Long-term adverse effects possibly related to MSC treatment Tumor formation (physical examination, plain x-ray, f/u MRI at 90 days after treatment), Aberrant connections (newly diagnosed seizure or arrhythmia)
measure: Exploration of biomarkers
time frame: During 90 days after the cell treatment
description: SDF(stromal cell-derived factor)-1ɑ (chemokine) S100ß (protection and regeneration) HIF(Hypoxia-inducible factor)-1 (preconditioning) Circulating MSCs and MSC-derived microparticles (CD105-CXCR4(C-X-C chemokine receptor type 4)-PS(phosphoserine)) BDNF (Brain-derived neurotrophic factor) levels and it's polymorphism, and VEGF (Vascular endothelial growth factor) levels
Resting-state functional MRI & Diffusion tensor imaging
arm group label: Mesenchymal stem cell treatment
arm group type: Experimental
arm group label: Standard treatment
arm group type: No Intervention
intervention type: Other
intervention name: Mesenchymal stem cell
description: intravenous transplantation of autologous mesenchymal stem cells expanded with autologous serum
arm group label: Mesenchymal stem cell treatment
criteria: 
gender: All
minimum age: 30 Years
maximum age: 75 Years
healthy volunteers: No
last name: Oh Young Bang, MD
role: Principal Investigator
affiliation: Samsung Medical Center
last name: Oh Young Bang, MD
phone: 82-10-3410-3599
email: nmboy@unitel.co.kr
last name: Sang Ae Park, RN
phone: 82-10-3410-0934
email: sa0124.park@samsung.com
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
country: Korea, Republic of
responsible party type: Principal Investigator
investigator affiliation: Samsung Medical Center
investigator full name: Oh Young Bang
investigator title: Associate Professor
mesh term: Stroke
mesh term: Ischemic Stroke