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

April 24, 2017 updated by: Oh Young Bang, Samsung Medical Center

Intravenous Administration of Autoserum-cultured Autologous Mesenchymal Stem Cells in Ischemic Stroke: A Single Center, Randomized, Open Label, Prospective, Phase 3 Study

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.

Study Overview

Status

Unknown

Conditions

Intervention / 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.

Study Type

Interventional

Enrollment (Anticipated)

60

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Korea, Republic of
      • Seoul, Korea, Republic of, 135710
        • Recruiting
        • Samsung Medical Center, Sungkyunkwan University School of Medicine
        • 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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

30 years to 75 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Mesenchymal stem cell treatment
Other: Mesenchymal stem cell
intravenous transplantation of autologous mesenchymal stem cells expanded with autologous serum
NO_INTERVENTION: Standard treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Categorical shift in modified Rankin scale (mRS)
Time Frame: 90 days after the cell treatment
Categorical shift in mRS at 90 days after the cell treatment
90 days after the cell treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change of National Institutes of Health stroke scale (NIHSS)
Time Frame: 90 days after the cell treatment
Change of NIHSS between pre- and post-treatment 90 days
90 days after the cell treatment
Early improvement of National Institutes of Health stroke scale (NIHSS)
Time Frame: 14 days after the cell treatment
≥5 points improvement or score of 0-2 on NIHSS score at 14 days after treatment
14 days after the cell treatment
Dichotomized modified Rankin scale (mRS)
Time Frame: 90 days after the cell treatment
mRS ≤2 at 90 days after treatment
90 days after the cell treatment
Change of modified Rankin scale (mRS)
Time Frame: 90 days after the cell treatment
Change of mRS between pre- and post-treatment 90 days
90 days after the cell treatment
Dichotomized modified Barthel index (mBI)
Time Frame: 90 days after the cell treatment
mBI ≥60 at 90 days after treatment
90 days after the cell treatment
Change of modified Barthel index (mBI)
Time Frame: 90 days after the cell treatment
Change of mBI between pre- and post-treatment 90 days
90 days after the cell treatment
Change of gross motor function
Time Frame: 90 days after the cell treatment
Change of Gross motor function (Motricity index and Fugl-Meyer assessment)between pre- and post-treatment 90 days
90 days after the cell treatment
Change of Fine motor function
Time Frame: 90 days after the cell treatment
Change of Fine motor function (Purdue Pegboard test and Box and block test) between pre- and post-treatment 90 days
90 days after the cell treatment
Change of Mobility
Time Frame: 90 days after the cell treatment
Change of Mobility (Functional ambulatory category and 10m-Gait speed) between pre- and post-treatment 90 days
90 days after the cell treatment
Change of mini-mental status exam (MMSE)
Time Frame: 90 days after the cell treatment
Change of MMSE between pre- and post-treatment 90 days
90 days after the cell treatment
Change of quality of life
Time Frame: 90 days after the cell treatment
Change of EuroQol 5d (EQ-5D) between pre- and post-treatment 90 days
90 days after the cell treatment
Safety outcome
Time Frame: During 90 days after the cell treatment
  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)
During 90 days after the cell treatment

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Exploration of biomarkers
Time Frame: During 90 days after the cell treatment

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
During 90 days after the cell treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Samsung Medical Center

Collaborators

Pharmicell Co., Ltd.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2012

Primary Completion (ANTICIPATED)

December 1, 2017

Study Completion (ANTICIPATED)

December 1, 2017

Study Registration Dates

First Submitted

October 25, 2012

First Submitted That Met QC Criteria

October 25, 2012

First Posted (ESTIMATE)

October 29, 2012

Study Record Updates

Last Update Posted (ACTUAL)

April 26, 2017

Last Update Submitted That Met QC Criteria

April 24, 2017

Last Verified

April 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2011-10-047

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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