Autologous Bone Marrow Mesenchymal Stem Cells (BMSCs) Transplantation in the Treatment of Ischemic Stroke

A Randomized, Open and Routine Parallel Controlled Clinical Study on the Safety and Efficacy of Autologous Bone Marrow Mesenchymal Stem Cells (BMSCs) Transplantation in the Treatment of Ischemic Stroke

This study is to evaluated the safety and efficacy of BMSCs transplantation in the treatment of ischemic stroke, so as to provide a basis for future clinical application of BMSCs transplantation in the treatment of ischemic stroke.

Study Overview

• Status: Recruiting
• Conditions: Ischemic Stroke
• Intervention / Treatment: Biological: Transplantation of self BMSCs

Detailed Description

1. Routine treatment:

   1.1. If arterial plaque is found, use lipid-lowering therapy (routine dose of atorvastatin or rosuvastatin). If no plaque is found, use atorvastatin or rosuvastatin based on the maintenance of normal blood lipid;

   1.2. If venous thrombosis or arterial plaques are found in the lower limbs, use dabigatran to prevent platelet aggregation; if no vascular problems are found in the lower limbs, use aspirin or clopidogrel to prevent platelet aggregation;

   1.3. During the treatment, cerebrovascular stenosis (non responsible vessels) can be treated intravascularly;

   1.4. The use of neurotrophic drugs is prohibited during the study;

   1.5. Elevated homocysteine was treated with mecobalamin and folic acid;

   1.6. Hypertension, diabetes and other basic diseases receive routine treatment, and the combined medication is recorded in the case report form.

2. Grouping:

2.1. BMSCs group: BMSCs were transplanted on the basis of routine treatment: the transplanted cells were injected intravenously and transplanted in two times, with a dose of 1 × 106 / kg body weight, each volume of 80ml ± 5ml, and the time interval between two transplants was 1 week;

2.2. Routine treatment group: only receiving routine treatment;

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Jiang Xiaodan; Phone Number: 18680288751; Email: jiangxd@smu.edu.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510220
      • Recruiting
      • Zhujiang Hospital of Southern Medical University
      • Contact: Jiang Xiao dan; Phone Number: 18680288751; Email: jiangxd@smu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients aged 18-65 years old in the rehabilitation period of cerebral infarction (including subacute stage, chronic stage and sequelae stage, with onset time ≤ 3 years), regardless of gender;
2. Definite cerebral infarction in the blood supply area of middle cerebral artery confirmed by imaging;
3. There are clear neurological deficits, such as motor and cognitive dysfunction (National Institutes of Health Stroke Scale 7 < NIHSS < 21 points);
4. Those who agree to take effective contraceptive measures during the study period, and women of childbearing age have negative pregnancy test;
5. Sign the informed consent of the patient and agree to participate in all visits, examinations and treatments as required by the study protocol.

Exclusion Criteria:

1. Lacunar cerebral infarction;
2. Acute cerebral infarction, onset time < 2 weeks;
3. Mild ischemic stroke or mild neurological impairment or severe ischemic stroke, with coma;
4. Patients with moyamoya disease, vascular malformation, hemangioma and carotid stenosis exceeding 70%;
5. Patients with severe heart valve disease or confirmed intractable atrial fibrillation;
6. Complicated with intracranial hemorrhage or tumor;
7. Patients with cerebral infarction caused by blood system diseases, or those with previous blood history or family history of blood diseases;
8. Any one of 5 items of hepatitis B virus (HBsAg, HBsAb, HBeAg, HBeAb, HBcAb), hepatitis C virus (HCV) antibody, human immunodeficiency virus (HIV) antibody and syphilis spiral physical examination;
9. Those with severe respiratory or circulatory system or liver and kidney dysfunction who cannot tolerate treatment and examination;
10. Severe febrile disease or viral disease in the past 12 weeks;
11. Malignant tumor;
12. Those who have a previous history of autoimmune diseases or a family history of autoimmune diseases;
13. Previous history of drug allergy;
14. Pregnant or lactating women;
15. Those who are participating or have participated in this study or participated in other clinical trials within 12 weeks before enrollment;
16. Other circumstances that the investigator considers inappropriate for participation in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Routine treatment group; No special measures were taken and routine treatment was adopted
Experimental: BMSCs group; BMSCs were transplanted on the basis of routine treatment: the transplanted cells were injected intravenously and transplanted in two times at a dose of 1 × 106/kg body weight, each volume was 80ml ± 5ml, and the time interval between two transplants was 1 week	Biological: Transplantation of self BMSCs; Bone marrow was collected, cultured in vitro and injected back into the body

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The difference in National Institutes of Health Stroke Scale (NIHSS) score from baseline after the first transplant.	The difference in National Institutes of Health Stroke Scale (NIHSS) score from baseline at week 96 ±30 days after the first transplant.	96 weeks ±30 days after the first transplantation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The difference from baseline in National Institutes of Health Stroke Scale (NIHSS) score after the first transplantation	The difference from baseline in National Institutes of Health Stroke Scale (NIHSS) score at 48 weeks ±15 days after the first transplantation	48 weeks ±15 days after the first transplantation
Improvement rate of the modified Barthel Index Rating Scale score from baseline after the first transplant	Improvement rate of the modified Barthel Index Rating Scale score from baseline at 48 weeks ±15 days after the first transplantation	48 weeks ±15 days after the first transplantation
Improvement rate of the modified Barthel Index Rating Scale score from baseline	Improvement rate of the modified Barthel Index Rating Scale score from baseline at 96 weeks ±30 days after the first transplant	96 weeks ±30 days after the first transplantation
Improvement rate of Fugl-Meyer scale score from baseline after the first transplantation	Improvement rate of Fugl-Meyer scale score from baseline at 48 weeks ±15 days after the first transplantation	48 weeks ±15 days after the first transplantation
Improvement rate of Fugl-Meyer scale score from baseline after the first transplantation	Improvement rate of Fugl-Meyer scale score from baseline at 96 weeks ±30 days after the first transplantation	96 weeks ±30 days after the first transplantation
Improvement rate of Simple Mental State Examination Scale (MMSE) score	Improvement rate of Simple Mental State Examination Scale (MMSE) score from baseline at 48 weeks ±15 days after the first transplantation	48 weeks ±15 days after the first transplantation
Improvement rate of Simple Mental State Examination Scale (MMSE) score	Improvement rate of Simple Mental State Examination Scale (MMSE) score from baseline at 96 weeks ±30 days after the first transplantation	96 weeks ±30 days after the first transplantation
The time course of the left abductor pollicis brevis and right abductor pollicis brevis of the motor evoked potential decreased from baseline after the first transplantation	The time course of the left abductor pollicis brevis and right abductor pollicis brevis of the motor evoked potential decreased from baseline at 48 weeks ±15 days after the first transplantation	48 weeks ±15 days after the first transplantation
The time course of the left abductor pollicis brevis and right abductor pollicis brevis of the motor evoked potential decreased from baseline after the first transplantation	The time course of the left abductor pollicis brevis and right abductor pollicis brevis of the motor evoked potential decreased from baseline at 96 weeks ±30 days after the first transplantation	96 weeks ±30 days after the first transplantation
MT increase rate from baseline in the left abductor Pollicis brevis and right abductor pollicis brevis of the motor evoked potential after the first transplantation	MT increase rate from baseline in the left abductor Pollicis brevis and right abductor pollicis brevis of the motor evoked potential at 48 weeks ±15 days after the first transplantation	48 weeks ±15 days after the first transplantation
MT increase rate from baseline in the left abductor Pollicis brevis and right abductor pollicis brevis of the motor evoked potential after the first transplantation	MT increase rate from baseline in the left abductor Pollicis brevis and right abductor pollicis brevis of the motor evoked potential at 96 weeks ±30 days after the first transplantation	96 weeks ±30 days after the first transplantation
The time course of the upper limb sensory evoked potential N9(left), N11(left), N20(left), N9(right), N11(right), N20(right) decreased from baseline after the first transplantation	The time course of the upper limb sensory evoked potential N9(left), N11(left), N20(left), N9(right), N11(right), N20(right) decreased from baseline at 48 weeks ±15 days after the first transplantation	48 weeks ±15 days after the first transplantation
The time course of the upper limb sensory evoked potential N9(left), N11(left), N20(left), N9(right), N11(right), N20(right) decreased from baseline after the first transplantation	The time course of the upper limb sensory evoked potential N9(left), N11(left), N20(left), N9(right), N11(right), N20(right) decreased from baseline at 96 weeks ±30 days after the first transplantation	96 weeks ±30 days after the first transplantation
Rate of increase from baseline amplitude of the upper limb sensory evoked potential N9(left), N11(left), N20(left), N9(right), N11(right), N20(right) after the first transplantation	Rate of increase from baseline amplitude of the upper limb sensory evoked potential N9(left), N11(left), N20(left), N9(right), N11(right), N20(right) at 48 weeks ±15 days after the first transplantation	48 weeks ±15 days after the first transplantation
Rate of increase from baseline amplitude of the upper limb sensory evoked potential N9(left), N11(left), N20(left), N9(right), N11(right), N20(right) after the first transplantation	Rate of increase from baseline amplitude of the upper limb sensory evoked potential N9(left), N11(left), N20(left), N9(right), N11(right), N20(right) at 96 weeks ±30 days after the first transplantation	96 weeks ±30 days after the first transplantation
Changes in CTA from baseline after the first transplantation	Changes in CTA from baseline at 48 weeks ±15 days after the first transplantation	48 weeks ±15 days after the first transplantation
Changes in CTA from baseline after the first transplantation	Changes in CTA from baseline at 96 weeks ±30 days after the first transplantation	96 weeks ±30 days after the first transplantation
Changes in CTP from baseline after the first transplantation	Changes in CTP from baseline at 96 weeks ±30 days after the first transplantation	96 weeks ±30 days after the first transplantation
Changes in CTP from baseline after the first transplantation	Changes in CTP from baseline at 48 weeks ±15 days after the first transplantation	48 weeks ±15 days after the first transplantation
Changes in mRS Scores from baseline after the first transplantation	Changes in mRS Scores from baseline at 48 weeks ±15 days after the first transplantation	48 weeks ±15 days after the first transplantation
Changes in mRS Scores from baseline after the first transplantation	Changes in mRS Scores from baseline at 96 weeks ±30 days after the first transplantation	96 weeks ±30 days after the first transplantation

Collaborators and Investigators

• Sponsor: Zhujiang Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 23, 2022
• Primary Completion (Anticipated): November 30, 2024
• Study Completion (Anticipated): December 31, 2024

Study Registration Dates

• First Submitted: August 24, 2022
• First Submitted That Met QC Criteria: May 6, 2023
• First Posted (Actual): May 9, 2023

Study Record Updates

• Last Update Posted (Actual): May 9, 2023
• Last Update Submitted That Met QC Criteria: May 6, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Ischemia; Infarction; Brain Infarction; Stroke; Ischemic Stroke; Ischemia; Cerebral Infarction
• Other Study ID Numbers: ZJYY.ZTGSJCZGXB-HBT-V2.3-CTP

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Not yet determined

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No