Effect of Mesenchymal Stem Cells(MSCs) Transplantation for Acute Cerebral Infarction Patients

Stroke, Ischemic Clinical Trial

Official title:

Effect of Human Umbilical Cord Mesenchymal Stem Cells(MSCs) Transplantation for on Prognosis of Acute Cerebral Infarction Patients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04093336
• Other study ID #: 2018-DFSC-002(V3)
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: January 13, 2019
• Est. completion date: December 30, 2024

Study information

• Verified date: April 2023
• Source: Shanghai East Hospital
• Contact: Gang Li, Doctor
• Phone: 0086-021-38804518-22106
• Email: ligang[@]tongji.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a placebo controlled, randomized, double blinded study including Phase 1 and Phase 2. Phase I study is a safety assessment and Phase 2 study is incline to assess effectiveness of MSCs. Potential subjects must be screened and consented before enrolled.

The primary objective of this study is to determine the effects of early intravenous infusion of allogeneic human umbilical cord mesenchymal stem cells (HucMSCs or MSCs used in the following section) for patients with acute ischemic stroke. Eligible patients will receive a single dose of MSCs or placebo within 24 hours after stroke. Patients will be followed for 2 years post infusion for safety and efficacy (change in neurological symptoms and quality of life). Assessments will occur during transplantation and at 3,7, 14 days and1,3, 6, 12, 18 and 24 months after infusions of stem cells.

Description:

In Phase 1 study, the eligible patients of acute cerebral infarction within 7 days after onset will be randomized to MSCs group or control group and receive intravenous MSCs 2 x 10^6/kg or placebo as a single dose, respectively. Each group will enroll 10 patients and patients will be followed for 2 years to observe the adverse events and evaluate the safety of MSCs for acute ischemic stroke patients.

The safety and preliminary effectiveness of MSCs in the treatment of acute cerebral infarction will be summarized after all patients of Phase 1 study were followed for 3 months post infusion, and the report will be submit to the academic committee and the ethics committee to evaluate before approval to begin the Phase 2 study.

In Phase 2 study, 100 patients with acute infarction within 24 hours after onset will be enrolled and randomized to MSCs group or control group. Patients will have baseline laboratory examinations and cerebral image (MRI or CTP). Enrolled patients will receive intravenous infusion of 2*10^6/kg MSCs or placebo for a single dose and follow for 24 months to assess the adverse events, neurological functional recovery and quality of life.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: December 30, 2024
• Est. primary completion date: December 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Acute ischemic stroke;

2. Age 18~80y;

3. 4=NIHSS score=18(including limb score=2)and modified Rankin scale 0-1 before this cerebral ischemic stroke;

4. patients and their families understand and will cooperate within the whole process of study, and sign informed consent;

5. any of following items:?acute cerebral infarction confirmed by cerebral CT perfusion or non-contrast computed tomographic scan < 7 days after onset or ?acute cerebral infarction confirmed by cerebral MR image < 7 days after onset

Exclusion Criteria:

1. accompanied by hematological disease, severe infection, liver dysfunction (ALT>3*ULN), kidney dysfunction (Scr >2*ULN), cardiac dysfunction (NYHA grade III or IV);

2. Disturbance of consciousness, mental illness, cognitive impairment and other diseases that may affect informed consent and evaluation of study.

3. Malignancy history or found to associate cancer after this stroke

4. Pregnant or lactating women, or women have fertility requirements within 2 years;

5. Accompanied by immunodeficiency diseases or autoimmune diseases;

6. Life expectancy is less than 2 years;

7. Participated in other clinical trial within 6 months;

8. Patients received Chinese traditional medicine after onset of this stroke;

9. Patients with allergic predisposition;

10. Mental implantation or other reasons cannot tolerate magnetic resonance imaging;

11. Cannot follow up regularly or unwilling to sign informed consent;

12. Other situations not suitable for enrollment judged by the researchers;

Related Conditions & MeSH terms

• Acute Stroke
• Brain Infarction
• Cerebral Infarction
• Infarction
• Infarction, Anterior Cerebral Artery
• Infarction, Middle Cerebral Artery
• Ischemic Stroke
• Stroke
• Stroke, Ischemic

Intervention

Biological:
• human umbilical cord mesenchymal stem cells
The MSCs was intravenous transplanted to acute cerebral infarction patients as a single dose.
• Placebo
Placebo

Other:
• standardized treatment
standardized treatment

Locations

Country	Name	City	State
China	Gang Li	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai East Hospital

Country where clinical trial is conducted

China, 

References & Publications (11)

Campbell BC, Mitchell PJ, Kleinig TJ, Dewey HM, Churilov L, Yassi N, Yan B, Dowling RJ, Parsons MW, Oxley TJ, Wu TY, Brooks M, Simpson MA, Miteff F, Levi CR, Krause M, Harrington TJ, Faulder KC, Steinfort BS, Priglinger M, Ang T, Scroop R, Barber PA, McGu — View Citation

Cao W, Li P. Effectiveness and Safety of Autologous Bone Marrow Stromal Cells Transplantation After Ischemic Stroke: A Meta-Analysis. Med Sci Monit. 2015 Jul 28;21:2190-5. doi: 10.12659/MSM.895081. — View Citation

Crigler L, Robey RC, Asawachaicharn A, Gaupp D, Phinney DG. Human mesenchymal stem cell subpopulations express a variety of neuro-regulatory molecules and promote neuronal cell survival and neuritogenesis. Exp Neurol. 2006 Mar;198(1):54-64. doi: 10.1016/j — View Citation

Donnan GA, Fisher M, Macleod M, Davis SM. Stroke. Lancet. 2008 May 10;371(9624):1612-23. doi: 10.1016/S0140-6736(08)60694-7. — View Citation

GBD 2013 Mortality and Causes of Death Collaborators. Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 201 — View Citation

Ikeda N, Nonoguchi N, Zhao MZ, Watanabe T, Kajimoto Y, Furutama D, Kimura F, Dezawa M, Coffin RS, Otsuki Y, Kuroiwa T, Miyatake S. Bone marrow stromal cells that enhanced fibroblast growth factor-2 secretion by herpes simplex virus vector improve neurolog — View Citation

Jauch EC, Saver JL, Adams HP Jr, Bruno A, Connors JJ, Demaerschalk BM, Khatri P, McMullan PW Jr, Qureshi AI, Rosenfield K, Scott PA, Summers DR, Wang DZ, Wintermark M, Yonas H; American Heart Association Stroke Council; Council on Cardiovascular Nursing; — View Citation

Lee RH, Pulin AA, Seo MJ, Kota DJ, Ylostalo J, Larson BL, Semprun-Prieto L, Delafontaine P, Prockop DJ. Intravenous hMSCs improve myocardial infarction in mice because cells embolized in lung are activated to secrete the anti-inflammatory protein TSG-6. C — View Citation

Ren G, Chen X, Dong F, Li W, Ren X, Zhang Y, Shi Y. Concise review: mesenchymal stem cells and translational medicine: emerging issues. Stem Cells Transl Med. 2012 Jan;1(1):51-8. doi: 10.5966/sctm.2011-0019. Epub 2011 Dec 7. — View Citation

Vu Q, Xie K, Eckert M, Zhao W, Cramer SC. Meta-analysis of preclinical studies of mesenchymal stromal cells for ischemic stroke. Neurology. 2014 Apr 8;82(14):1277-86. doi: 10.1212/WNL.0000000000000278. Epub 2014 Mar 7. — View Citation

Zhao Y, Yao Z, D'Souza W, Zhu C, Chun H, Zhuoga C, Zhang Q, Hu X, Zhou D. An epidemiological survey of stroke in Lhasa, Tibet, China. Stroke. 2010 Dec;41(12):2739-43. doi: 10.1161/STROKEAHA.110.586669. Epub 2010 Oct 21. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	adverse events	include tumorigenesis, death, pulmonary embolism, allergy, newly cerebrovascular events and other adverse events to evaluate the safety of MSCs for acute ischemic stroke patients	24 months post transplantation
Secondary	the National Institutes of Health Stroke Scale (NIHSS) of 3 months	The NIHSS neurologic examination includes 15 individual elements that measure motor and sensory function, language and speech production, vision, level of consciousness and attention, and neglect. The scores of each element are summed (range from 0 to 42) to evaluate the severity of neurological deficits. The more higher score means the more severe neurological dysfunction.	3 months post transplantation
Secondary	the Barthel index (BI) of 3 months	The BI (range from 0 to 100) are used to assess the difference of activities of daily living between two groups. the score =40 means severe dependence, score 41~60 means moderate dependence, score 61~99 means mild dependence and score 100 means independence.	3 months post transplantation