The STem Cell Application Researches and Trials In NeuroloGy-2 (STARTING-2) Study

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Samsung Medical Center
Sponsor:
Collaborator:
Pharmicell Co., Ltd.
Information provided by (Responsible Party):
Oh Young Bang, Samsung Medical Center
ClinicalTrials.gov Identifier:
NCT01716481
First received: October 25, 2012
Last updated: May 8, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Stroke, Ischemic
Other: Mesenchymal stem cell
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Intravenous Administration of Autoserum-cultured Autologous Mesenchymal Stem Cells in Ischemic Stroke: A Single Center, Randomized, Open Label, Prospective, Phase 3 Study

Resource links provided by NLM:


Further study details as provided by Samsung Medical Center:

Primary Outcome Measures:
  • Categorical shift in modified Rankin scale (mRS) [ Time Frame: 90 days after the cell treatment ] [ Designated as safety issue: No ]
    Categorical shift in mRS at 90 days after the cell treatment


Secondary Outcome Measures:
  • Change of National Institutes of Health stroke scale (NIHSS) [ Time Frame: 90 days after the cell treatment ] [ Designated as safety issue: No ]
    Change of NIHSS between pre- and post-treatment 90 days

  • Early improvement of National Institutes of Health stroke scale (NIHSS) [ Time Frame: 14 days after the cell treatment ] [ Designated as safety issue: No ]
    ≥5 points improvement or score of 0-2 on NIHSS score at 14 days after treatment

  • Dichotomized modified Rankin scale (mRS) [ Time Frame: 90 days after the cell treatment ] [ Designated as safety issue: No ]
    mRS ≤2 at 90 days after treatment

  • Change of modified Rankin scale (mRS) [ Time Frame: 90 days after the cell treatment ] [ Designated as safety issue: No ]
    Change of mRS between pre- and post-treatment 90 days

  • Dichotomized modified Barthel index (mBI) [ Time Frame: 90 days after the cell treatment ] [ Designated as safety issue: No ]
    mBI ≥60 at 90 days after treatment

  • Change of modified Barthel index (mBI) [ Time Frame: 90 days after the cell treatment ] [ Designated as safety issue: No ]
    Change of mBI between pre- and post-treatment 90 days

  • Change of gross motor function [ Time Frame: 90 days after the cell treatment ] [ Designated as safety issue: No ]
    Change of Gross motor function (Motricity index and Fugl-Meyer assessment)between pre- and post-treatment 90 days

  • Change of Fine motor function [ Time Frame: 90 days after the cell treatment ] [ Designated as safety issue: No ]
    Change of Fine motor function (Purdue Pegboard test and Box and block test) between pre- and post-treatment 90 days

  • Change of Mobility [ Time Frame: 90 days after the cell treatment ] [ Designated as safety issue: No ]
    Change of Mobility (Functional ambulatory category and 10m-Gait speed) between pre- and post-treatment 90 days

  • Change of mini-mental status exam (MMSE) [ Time Frame: 90 days after the cell treatment ] [ Designated as safety issue: No ]
    Change of MMSE between pre- and post-treatment 90 days

  • Change of quality of life [ Time Frame: 90 days after the cell treatment ] [ Designated as safety issue: No ]
    Change of EuroQol 5d (EQ-5D) between pre- and post-treatment 90 days

  • Safety outcome [ Time Frame: During 90 days after the cell treatment ] [ Designated as safety issue: Yes ]
    1. Death: All causes of death
    2. Recurrence: Recurrent stroke or transient ischemic attack
    3. 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).

    4. 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)


Other Outcome Measures:
  • Exploration of biomarkers [ Time Frame: During 90 days after the cell treatment ] [ Designated as safety issue: No ]

    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



Estimated Enrollment: 60
Study Start Date: November 2012
Estimated Study Completion Date: February 2016
Estimated Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Mesenchymal stem cell treatment Other: Mesenchymal stem cell
intravenous transplantation of autologous mesenchymal stem cells expanded with autologous serum
No Intervention: Standard treatment

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   30 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Men or women (women must be of non-child bearing potential), age 30-75 yrs.
  2. Have a stroke that is observed within 90 days of the onset of symptoms
  3. Radiologically

    1. Relevant lesions within the middle cerebral artery territory (MCA) as assessed using diffusion-weighted imaging (DWI).
    2. The maximum diameter of the stroke region in any dimension must be ≥15 mm.
    3. Not involving more than a half of the ipsilateral periventricular zone
  4. Clinically (National Institutes of Health stroke scale, NIHSS)

    1. Moderate-to severe persistent neurologic deficit (NIHSS of 6-21 inclusive)
    2. New onset of extremity paresis on the affected side, defined as a score of 2-4 on the NIHSS Motor Arm (item 5) or Leg (item 6) question.
    3. Must be alert or drowsy but easily arousable as defined by score of 0-1 on the NIHSS Level of Consciousness question (item 1).
    4. "Slow recovery" defined as Change in NIHSS ≤1 point/3 days
  5. Willingness

    1. Reasonable likelihood of receiving standard physical, occupational and speech rehabilitation therapy as indicated for the post stroke deficits.
    2. Able to participate in the evaluation process to the point of accurate assessment.
    3. Willing and able to comply with scheduled visits, lifestyle guidelines, treatment plan, laboratory tests, and other study procedures.
    4. Evidence of a personally signed and dated informed consent document.

Exclusion Criteria:

  1. Presence of significant disability prior to the current stroke. Significant disability is defined as having a pre-stroke modified Rankin score of 2 or more.
  2. Have a stroke that is either

    1. lacunar infarction
    2. Hematologic cause of stroke
    3. Recurrent or progressive stroke within 1 week at the time of screening.
  3. Hematologic disorders or bone marrow suppression.
  4. Have a severe medical illness

    1. Severe heart failure
    2. Severe febrile illness
    3. Hepatic or renal dysfunction
    4. Active cancer
    5. Any evidence of chronic co-morbid condition or unstable acute systemic illnesses which, in the opinion of the investigator, could shorten the subject's survival or limit ability to complete the study.
  5. Presence of human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), or syphilis on admission blood tests
  6. Presence of depression that is active and not adequately controlled such that it interfere with major activities of daily living immediately prior to the current stroke.
  7. Presence of dementia prior to the current stroke that is likely to confound clinical evaluation.
  8. Pregnant females as determined by positive urine human chorionic gonadotropin (hCG) test or lactating females.
  9. Subjects considered unwilling or unable to comply with the procedures and study visit schedule outlined in the protocol
  10. Subjects unwilling to undergo bone marrow aspiration
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01716481

Contacts
Contact: Oh Young Bang, MD 82-10-3410-3599 nmboy@unitel.co.kr
Contact: Sang Ae Park, RN 82-10-3410-0934 sa0124.park@samsung.com

Locations
Korea, Republic of
Samsung Medical Center, Sungkyunkwan University School of Medicine Recruiting
Seoul, Korea, Republic of, 135710
Contact: Suk Jae Kim, MD    82-2-3410-1895    sukjae.kim@gmail.com   
Principal Investigator: Oh Young Bang, MD         
Sub-Investigator: Suk Jae Kim, MD         
Sub-Investigator: Gyeong Joon Moon, PhD         
Sub-Investigator: Yun-Hee Kim, MD         
Sub-Investigator: Sookyoung Ryoo, MD         
Sub-Investigator: Yeon Hee Cho, MS         
Sub-Investigator: Yoon Mi Kang, PhD         
Sub-Investigator: Yong Man Kim, PhD         
Sub-Investigator: Hyun Soo Kim, MD         
Sub-Investigator: Jun Ho Jang, MD         
Sub-Investigator: Won Hyuk Chang, MD         
Sub-Investigator: Dong Hee Kim, BA         
Sub-Investigator: Ji-Yoon Nam, BA         
Sub-Investigator: Ji Hyun Lee, BA         
Sub-Investigator: Gyeong-Moon Kim, MD         
Sub-Investigator: Chin-Sang Chung, MD         
Sub-Investigator: Kwang Ho Lee, MD         
Sponsors and Collaborators
Samsung Medical Center
Pharmicell Co., Ltd.
Investigators
Principal Investigator: Oh Young Bang, MD Samsung Medical Center
  More Information

No publications provided by Samsung Medical Center

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Oh Young Bang, Associate Professor, Samsung Medical Center
ClinicalTrials.gov Identifier: NCT01716481     History of Changes
Other Study ID Numbers: 2011-10-047
Study First Received: October 25, 2012
Last Updated: May 8, 2014
Health Authority: South Korea: Institutional Review Board
South Korea: Food and Drug Administration

Keywords provided by Samsung Medical Center:
Stroke
Mesenchymal stem cells
Stem cells
Neurogenesis

Additional relevant MeSH terms:
Ischemia
Stroke
Cerebral Infarction
Pathologic Processes
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Brain Infarction
Brain Ischemia

ClinicalTrials.gov processed this record on July 26, 2014