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

Phase 3

• Conditions: Stroke, Ischemic
• Interventions: Other: Mesenchymal stem cell

• Registration Number: NCT01716481
• Lead Sponsor: Samsung Medical Center

Brief Summary

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.

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2012-10-25
• Study First Submitted QC: 2012-10-25
• Study First Posted: 2012-10-29
• Study Start: 2012-11
• Status Verified: 2017-04
• Last Update Submitted: 2017-04-24
• Last Update Posted: 2017-04-26
• Primary Completion: 2017-12
• Study Completion: 2017-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 60

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.

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Mesenchymal stem cell treatment	Mesenchymal stem cell	-

Primary Outcome Measures

Name	Time	Method
Categorical shift in modified Rankin scale (mRS)	90 days after the cell treatment	Categorical shift in mRS at 90 days after the cell treatment

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Samsung Medical Center, Sungkyunkwan University School of Medicine; 🇰🇷 Seoul, Korea, Republic of