Back to resultsThe STem Cell Application Researches and Trials In NeuroloGy-2 (STARTING-2) Study (STARTING-2)
Primary Purpose
Stroke, Ischemic
Status
Unknown status
Phase
Phase 3
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Mesenchymal stem cell
Sponsored by
About this trial
This is an interventional treatment trial for Stroke, Ischemic focused on measuring Stroke, Mesenchymal stem cells, Stem cells, Neurogenesis
Eligibility Criteria
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
Sites / Locations
- Samsung Medical Center, Sungkyunkwan University School of MedicineRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
Mesenchymal stem cell treatment
Standard treatment
Arm Description
Outcomes
Primary Outcome Measures
Categorical shift in modified Rankin scale (mRS)
Categorical shift in mRS at 90 days after the cell treatment
Secondary Outcome Measures
Change of National Institutes of Health stroke scale (NIHSS)
Change of NIHSS between pre- and post-treatment 90 days
Early improvement of National Institutes of Health stroke scale (NIHSS)
≥5 points improvement or score of 0-2 on NIHSS score at 14 days after treatment
Dichotomized modified Rankin scale (mRS)
mRS ≤2 at 90 days after treatment
Change of modified Rankin scale (mRS)
Change of mRS between pre- and post-treatment 90 days
Dichotomized modified Barthel index (mBI)
mBI ≥60 at 90 days after treatment
Change of modified Barthel index (mBI)
Change of mBI between pre- and post-treatment 90 days
Change of gross motor function
Change of Gross motor function (Motricity index and Fugl-Meyer assessment)between pre- and post-treatment 90 days
Change of Fine motor function
Change of Fine motor function (Purdue Pegboard test and Box and block test) between pre- and post-treatment 90 days
Change of Mobility
Change of Mobility (Functional ambulatory category and 10m-Gait speed) between pre- and post-treatment 90 days
Change of mini-mental status exam (MMSE)
Change of MMSE between pre- and post-treatment 90 days
Change of quality of life
Change of EuroQol 5d (EQ-5D) between pre- and post-treatment 90 days
Safety outcome
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)
Full Information
NCT ID
NCT01716481
First Posted
October 25, 2012
Last Updated
April 24, 2017
Sponsor
Samsung Medical Center
Collaborators
Pharmicell Co., Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT01716481
Brief Title
The STem Cell Application Researches and Trials In NeuroloGy-2 (STARTING-2) Study
Acronym
STARTING-2
Official Title
Intravenous Administration of Autoserum-cultured Autologous Mesenchymal Stem Cells in Ischemic Stroke: A Single Center, Randomized, Open Label, Prospective, Phase 3 Study
Study Type
Interventional
2. Study Status
Record Verification Date
April 2017
Overall Recruitment Status
Unknown status
Study Start Date
November 2012 (undefined)
Primary Completion Date
December 2017 (Anticipated)
Study Completion Date
December 2017 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Samsung Medical Center
Collaborators
Pharmicell Co., Ltd.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stroke, Ischemic
Keywords
Stroke, Mesenchymal stem cells, Stem cells, Neurogenesis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
60 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Mesenchymal stem cell treatment
Arm Type
Experimental
Arm Title
Standard treatment
Arm Type
No Intervention
Intervention Type
Other
Intervention Name(s)
Mesenchymal stem cell
Intervention Description
intravenous transplantation of autologous mesenchymal stem cells expanded with autologous serum
Primary Outcome Measure Information:
Title
Categorical shift in modified Rankin scale (mRS)
Description
Categorical shift in mRS at 90 days after the cell treatment
Time Frame
90 days after the cell treatment
Secondary Outcome Measure Information:
Title
Change of National Institutes of Health stroke scale (NIHSS)
Description
Change of NIHSS between pre- and post-treatment 90 days
Time Frame
90 days after the cell treatment
Title
Early improvement of National Institutes of Health stroke scale (NIHSS)
Description
≥5 points improvement or score of 0-2 on NIHSS score at 14 days after treatment
Time Frame
14 days after the cell treatment
Title
Dichotomized modified Rankin scale (mRS)
Description
mRS ≤2 at 90 days after treatment
Time Frame
90 days after the cell treatment
Title
Change of modified Rankin scale (mRS)
Description
Change of mRS between pre- and post-treatment 90 days
Time Frame
90 days after the cell treatment
Title
Dichotomized modified Barthel index (mBI)
Description
mBI ≥60 at 90 days after treatment
Time Frame
90 days after the cell treatment
Title
Change of modified Barthel index (mBI)
Description
Change of mBI between pre- and post-treatment 90 days
Time Frame
90 days after the cell treatment
Title
Change of gross motor function
Description
Change of Gross motor function (Motricity index and Fugl-Meyer assessment)between pre- and post-treatment 90 days
Time Frame
90 days after the cell treatment
Title
Change of Fine motor function
Description
Change of Fine motor function (Purdue Pegboard test and Box and block test) between pre- and post-treatment 90 days
Time Frame
90 days after the cell treatment
Title
Change of Mobility
Description
Change of Mobility (Functional ambulatory category and 10m-Gait speed) between pre- and post-treatment 90 days
Time Frame
90 days after the cell treatment
Title
Change of mini-mental status exam (MMSE)
Description
Change of MMSE between pre- and post-treatment 90 days
Time Frame
90 days after the cell treatment
Title
Change of quality of life
Description
Change of EuroQol 5d (EQ-5D) between pre- and post-treatment 90 days
Time Frame
90 days after the cell treatment
Title
Safety outcome
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)
Time Frame
During 90 days after the cell treatment
Other Pre-specified Outcome Measures:
Title
Exploration of biomarkers
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
Time Frame
During 90 days after the cell treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
30 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Oh Young Bang, MD
Phone
82-10-3410-3599
Email
nmboy@unitel.co.kr
First Name & Middle Initial & Last Name or Official Title & Degree
Sang Ae Park, RN
Phone
82-10-3410-0934
Email
sa0124.park@samsung.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Oh Young Bang, MD
Organizational Affiliation
Samsung Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Samsung Medical Center, Sungkyunkwan University School of Medicine
City
Seoul
ZIP/Postal Code
135710
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Suk Jae Kim, MD
Phone
82-2-3410-1895
Email
sukjae.kim@gmail.com
First Name & Middle Initial & Last Name & Degree
Oh Young Bang, MD
First Name & Middle Initial & Last Name & Degree
Suk Jae Kim, MD
First Name & Middle Initial & Last Name & Degree
Gyeong Joon Moon, PhD
First Name & Middle Initial & Last Name & Degree
Yun-Hee Kim, MD
First Name & Middle Initial & Last Name & Degree
Sookyoung Ryoo, MD
First Name & Middle Initial & Last Name & Degree
Yeon Hee Cho, MS
First Name & Middle Initial & Last Name & Degree
Yoon Mi Kang, PhD
First Name & Middle Initial & Last Name & Degree
Yong Man Kim, PhD
First Name & Middle Initial & Last Name & Degree
Hyun Soo Kim, MD
First Name & Middle Initial & Last Name & Degree
Jun Ho Jang, MD
First Name & Middle Initial & Last Name & Degree
Won Hyuk Chang, MD
First Name & Middle Initial & Last Name & Degree
Dong Hee Kim, BA
First Name & Middle Initial & Last Name & Degree
Ji-Yoon Nam, BA
First Name & Middle Initial & Last Name & Degree
Ji Hyun Lee, BA
First Name & Middle Initial & Last Name & Degree
Gyeong-Moon Kim, MD
First Name & Middle Initial & Last Name & Degree
Chin-Sang Chung, MD
First Name & Middle Initial & Last Name & Degree
Kwang Ho Lee, MD
12. IPD Sharing Statement
Citations:
PubMed Identifier
35341320
Citation
Bang OY, Kim EH, Cho YH, Oh MJ, Chung JW, Chang WH, Kim YH, Yang SW, Chopp M. Circulating Extracellular Vesicles in Stroke Patients Treated With Mesenchymal Stem Cells: A Biomarker Analysis of a Randomized Trial. Stroke. 2022 Jul;53(7):2276-2286. doi: 10.1161/STROKEAHA.121.036545. Epub 2022 Mar 28.
Results Reference
derived
PubMed Identifier
34583525
Citation
Lee J, Chang WH, Chung JW, Kim SJ, Kim SK, Lee JS, Sohn SI, Kim YH, Bang OY; STARTING-2 Collaborators. Efficacy of Intravenous Mesenchymal Stem Cells for Motor Recovery After Ischemic Stroke: A Neuroimaging Study. Stroke. 2022 Jan;53(1):20-28. doi: 10.1161/STROKEAHA.121.034505. Epub 2021 Sep 29.
Results Reference
derived
PubMed Identifier
33472925
Citation
Chung JW, Chang WH, Bang OY, Moon GJ, Kim SJ, Kim SK, Lee JS, Sohn SI, Kim YH; STARTING-2 Collaborators. Efficacy and Safety of Intravenous Mesenchymal Stem Cells for Ischemic Stroke. Neurology. 2021 Feb 16;96(7):e1012-e1023. doi: 10.1212/WNL.0000000000011440. Epub 2021 Jan 20.
Results Reference
derived
PubMed Identifier
24083670
Citation
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.
Results Reference
derived
Learn more about this trial
The STem Cell Application Researches and Trials In NeuroloGy-2 (STARTING-2) Study
We'll reach out to this number within 24 hrs