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

Tracking Information
First Submitted Date ICMJE	October 25, 2012
First Posted Date ICMJE	October 29, 2012
Last Update Posted Date	April 26, 2017
Study Start Date ICMJE	November 2012
Estimated Primary Completion Date	December 2017 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: October 25, 2012)	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
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT01716481 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: October 31, 2012)	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; 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; Dichotomized modified Rankin scale (mRS) [ Time Frame: 90 days after the cell treatment ]mRS ≤2 at 90 days after 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; Dichotomized modified Barthel index (mBI) [ Time Frame: 90 days after the cell treatment ]mBI ≥60 at 90 days after 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; 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; 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; 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; 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; 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; Safety outcome [ Time Frame: During 90 days after the cell treatment ] 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)
Original Secondary Outcome Measures ICMJE; (submitted: October 25, 2012)	Change of NIH stroke scale (NIHSS) [ Time Frame: 90 days after the cell treatment ]Change of NIHSS between pre- and post-treatment 90 days; Early improvement of NIH 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; Dichotomized modified Rankin scale (mRS) [ Time Frame: 90 days after the cell treatment ]mRS ≤2 at 90 days after 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; Dichotomized modified Barthel index (mBI) [ Time Frame: 90 days after the cell treatment ]mBI ≥60 at 90 days after 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; 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; 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; 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; 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; 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; Safety outcome [ Time Frame: During 90 days after the cell treatment ] 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)
Current Other Outcome Measures ICMJE; (submitted: October 31, 2012)	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
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	The STem Cell Application Researches and Trials In NeuroloGy-2 (STARTING-2) Study
Official Title ICMJE	Intravenous Administration of Autoserum-cultured Autologous Mesenchymal Stem Cells in Ischemic Stroke: A Single Center, Randomized, Open Label, Prospective, Phase 3 Study
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.
Study Type ICMJE	Interventional
Study Phase	Phase 3
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Stroke, Ischemic
Intervention ICMJE	Other: Mesenchymal stem cell; intravenous transplantation of autologous mesenchymal stem cells expanded with autologous serum
Study Arms	Experimental: Mesenchymal stem cell treatment Intervention: Other: Mesenchymal stem cell; No Intervention: Standard treatment
Publications *	Kim SJ, Moon GJ, Chang WH, Kim YH, Bang OY; STARTING-2 (STem cell Application Researches and Trials In NeuroloGy-2) collaborators. Intravenous transplantation of mesenchymal stem cells preconditioned with early phase stroke serum: current evidence and study protocol for a randomized trial. Trials. 2013 Oct 1;14:317. doi: 10.1186/1745-6215-14-317.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Recruiting
Estimated Enrollment ICMJE; (submitted: October 25, 2012)	60
Original Estimated Enrollment ICMJE	Same as current
Estimated Study Completion Date	December 2017
Estimated Primary Completion Date	December 2017 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Men or women (women must be of non-child bearing potential), age 30-75 yrs.; Have a stroke that is observed within 90 days of the onset of symptoms; Radiologically Relevant lesions within the middle cerebral artery territory (MCA) as assessed using diffusion-weighted imaging (DWI). The maximum diameter of the stroke region in any dimension must be ≥15 mm. Not involving more than a half of the ipsilateral periventricular zone; Clinically (National Institutes of Health stroke scale, NIHSS) Moderate-to severe persistent neurologic deficit (NIHSS of 6-21 inclusive) 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. Must be alert or drowsy but easily arousable as defined by score of 0-1 on the NIHSS Level of Consciousness question (item 1). "Slow recovery" defined as Change in NIHSS ≤1 point/3 days; Willingness Reasonable likelihood of receiving standard physical, occupational and speech rehabilitation therapy as indicated for the post stroke deficits. Able to participate in the evaluation process to the point of accurate assessment. Willing and able to comply with scheduled visits, lifestyle guidelines, treatment plan, laboratory tests, and other study procedures. Evidence of a personally signed and dated informed consent document. Exclusion Criteria: 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.; Have a stroke that is either lacunar infarction Hematologic cause of stroke Recurrent or progressive stroke within 1 week at the time of screening.; Hematologic disorders or bone marrow suppression.; Have a severe medical illness Severe heart failure Severe febrile illness Hepatic or renal dysfunction Active cancer 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.; Presence of human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), or syphilis on admission blood tests; 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.; Presence of dementia prior to the current stroke that is likely to confound clinical evaluation.; Pregnant females as determined by positive urine human chorionic gonadotropin (hCG) test or lactating females.; Subjects considered unwilling or unable to comply with the procedures and study visit schedule outlined in the protocol; Subjects unwilling to undergo bone marrow aspiration
Sex/Gender	Sexes Eligible for Study: All
Ages	30 Years to 75 Years (Adult, Older Adult)
Accepts Healthy Volunteers	No
Contacts ICMJE	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
Listed Location Countries ICMJE	Korea, Republic of
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01716481
Other Study ID Numbers ICMJE	2011-10-047
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Oh Young Bang, Samsung Medical Center
Study Sponsor ICMJE	Samsung Medical Center
Collaborators ICMJE	Pharmicell Co., Ltd.
Investigators ICMJE	Principal Investigator: Oh Young Bang, MD Samsung Medical Center
PRS Account	Samsung Medical Center
Verification Date	April 2017
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP