Stem Cell Therapy for Intracerebral Hemorrhage

Clinical Research on Umbilical Cord Mesenchymal Stem Cells Therapy for Patients with Subacute Intracerebral Hemorrhage

Intracerebral hemorrhage (ICH) is a common condition with high morbidity, mortality, and disability. The current treatments for ICH primarily include surgical and pharmacological interventions. For large hematomas, surgical options such as craniotomy, debridement, decompression, and minimally invasive hematoma aspiration may be performed. Pharmacological treatments are mainly symptomatic. Despite timely and standardized surgical or pharmacological interventions, many patients with ICH still experience significant sequelae, which severely affect their quality of life and place a substantial burden on both families and society. Currently, there are limited drugs available specifically for the treatment of ICH.

In recent years, stem cell therapy has gained attention as a promising treatment for neurological diseases. Human umbilical cord mesenchymal stem cells (UC-MSCs) are multifunctional stem cells with properties such as self-renewal, multidirectional differentiation potential, tissue repair, immunomodulation, and anti-inflammatory effects. Studies have shown that intravenous transplantation of UC-MSCs is safe, and their application in the treatment of ICH can reduce hematoma volume, attenuate cerebral edema and inflammation, and promote the recovery of neurological function. These findings offer a novel therapeutic strategy for ICH.

The purpose of this clinical trial is to evaluate the safety and efficacy of UC-MSCs transplantation in patients with subacute intracerebral hemorrhage, and providing a potential new therapeutic approach for this challenging condition.

Study Overview

• Status: Not yet recruiting
• Conditions: Intracerebral Hemorrhage; Mesenchymal Stem Cell
• Intervention / Treatment: Biological: Device: Phase Ⅰ Dose Level 1; Biological: Device: Phase Ⅰ Dose Level 2; Biological: Device: Phase Ⅰ Dose Level 3; Biological: Device: Phase II MTD in Phase I; Biological: Device: Phase II lower than the MTD in Phase I

Detailed Description

This clinical trial is divided into two phases: Phase I and Phase II. The Phase I clinical trial is a single-center, open-label, dose-escalation study. It follows a 3+3 dose-escalation design and includes the following phases: screening/baseline phase, stem cell treatment phase, safety and tolerability observation phase, and follow-up phase, with a total of 10 visits. The primary focus of Phase I is to assess the safety of stem cell treatment. There are three dose groups, with at least 3 subjects in each group. Each subject will receive a cell dose of 1×10^6 cells/kg, 2×10^6 cells/kg, or 4×10^6 cells/kg. Phase I will enroll patients with subacute intracerebral hemorrhage who meet all inclusion and exclusion criteria. In line with the 3+3 dose-escalation design, human umbilical cord mesenchymal stem cells (UC-MSCs) will be intravenously administered at the designated doses at specific time points. The study will then observe both the primary and secondary safety endpoints following transplantation.

The Phase II clinical trial is also a single-center, open-label study. It is an exploratory efficacy study, consisting of a screening/baseline phase, stem cell treatment phase, and follow-up phase, with 8 visits in total. The primary objective of Phase II is to evaluate the safety and efficacy of UC-MSCs in the treatment of subacute intracerebral hemorrhage. The Phase II trial will consist of two groups, each with 15 subjects, for a total of 30 participants. The specific number of cells to be transplanted will be determined based on the findings from Phase I. UC-MSCs or saline will be intravenously infused into the subjects at designated time points, and visits will be scheduled according to the study plan. The primary safety and efficacy endpoints, as well as secondary endpoints, will be closely monitored after transplantation.

• Study Type: Interventional
• Enrollment (Estimated): 39
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Zhouping Tang, M.D.; Phone Number: +86-18071423962; Email: ddjtzp@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age 18-65 years old, gender is not limited.
2. Clinically confirmed intracerebral hemorrhage during the subacute period (3 days-10 days after onset).
3. CT confirmed as cerebral parenchymal hemorrhage, ABC/2 method to calculate the episodic hemorrhage volume of 15-30 mL (ABC/2 method hematoma volume calculation formula V (cm3) =A×B×C×1/2, A is the longest diameter of the largest level of the hematoma in the horizontal position of the CT scan (cm), B is the widest diameter of the hematoma in this plane perpendicular to the A (cm), C is the thickness of the hematoma appearing in the CT film (cm)).
4. Blood biochemical indexes meet the following conditions: 1) good coagulation function, international normalized ratio (INR) <2; 2) alachlor aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 times the upper limit of the normal value, and total bilirubin <2 times the upper limit of the normal value; 3) creatinine clearance >50 mL/min; 4) hemoglobin >90 g/L; 5) absolute neutrophil value (ANC) ≥ 1.5×10^9/L, absolute lymphocyte count ≥0.4×10^9/L, platelet count ≥80×10^9/L, and albumin >25g/L; 6) procalcitonin (PCT) ≤2ng/mL.
5. National Institutes of Health Stroke Scale score (NIHSS) ≥5 and ≤20.
6. Pre-onset modified Ranking Scale score (mRS) ≤1.
7. Glasgow Coma Score (GCS) ≥9 points and ≥3 points on a single item.
8. Good compliance, signed informed consent by the person and/or legal guardian and able to receive follow-up visits at the specified time.

Exclusion Criteria:

1. Brain midline deviation >10 mm or brain hernia formation.
2. Patients who have undergone or intend to undergo surgical treatment to remove hematoma.
3. Secondary intracerebral hemorrhage caused by traumatic brain injury, arteriovenous malformation, intracranial aneurysm, coagulation disorders, hemorrhagic transformation after cerebral infarction, or tumors.
4. Suffering from malignant tumors, autoimmune diseases (including but not limited to systemic lupus erythematosus, systemic vasculitis, etc.), hemorrhagic predisposition diseases (including all kinds of hereditary hemorrhagic disorders and acquired hemorrhagic diseases), malignant cardiac arrhythmia, cardiac insufficiency (BNP ≥1000pg/mL or left ventricular ejection fraction ≤40%), acute myocardial infarction, acute or severe infectious diseases (such as intracranial infection, severe pneumonia, sepsis, etc.) and other serious diseases that may aggravate the condition and affect the assessment of efficacy.
5. Allergy or intolerance to stem cell preparations or related medicines that need to be used in the infusion process, such as saline preparations and hormone preparations.
6. Pregnant or lactating women.
7. History of stroke disease with sequelae in the last 1 year, NIHSS score ≥ 6.
8. Subarachnoid hemorrhage, primary ventricular hemorrhage, pharmacological hemorrhagic stroke.
9. Unstable vital signs, including combined respiratory abnormalities (respiratory rate <12 breaths/min or >24 breaths/min, oxygen saturation ≤90%), hyperthermia (axillary temperature >39 ℃), blood pressure ≥180/100 mmHg after antihypertensive treatment, blood glucose >20 mmol/L.
10. Those who are participating in other clinical trials.
11. Previous history of epilepsy or current use of antiepileptic drugs.
12. Unable to accept all laboratory tests and imaging tests designed by the program due to metal implants or pacemakers in the body.
13. Inability to complete the follow-up program as required.
14. Patients or their legal guardians are unwilling to sign the written informed consent.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PhaseⅠclinical trial: 3+3 dose-escalation design; The Phase I clinical trial is a 3+3 dose-escalation trial, with three dose groups, each including at least 3 subjects. The trial begins with the low-dose group. If the dose-limiting toxicity (DLT) assessment during the observation period meets the criteria of the 3+3 dose-escalation design, enrollment will proceed to the next higher dose group. Each subject will receive one dose of human umbilical cord mesenchymal stem cells (UC-MSCs) therapy, in addition to the standard treatment for intracerebral hemorrhage.	Biological: Device: Phase Ⅰ Dose Level 1; Patients in the first dose level will receive a cell dose of 1×10^6 cells/kg.; Biological: Device: Phase Ⅰ Dose Level 2; Patients in the second dose level will receive a cell dose of 2×10^6 cells/kg.; Biological: Device: Phase Ⅰ Dose Level 3; Patients in the third dose level will receive a cell dose of 4×10^6 cells/kg. Based on these findings, the maximum tolerated dose (MTD) will be determined.
Experimental: Phase Ⅱ clinical trial: MTD group; The Phase II clinical trial included two groups. The dose of UC-MSCs received in each group patients will be determined based on the phase I results. One of the two groups subjects received the MTD obtained in phase I, and the other group subjects received a dose lower than the MTD. Each subject in the Phase II clinical trial received three dose of stem cell therapies after enrollment.The second therapy is 7 days after the first therapy, and the third therapy is 7 days after the second therapy.	Biological: Device: Phase II MTD in Phase I; This group subjects received the MTD obtained in phase I.
Experimental: Phase Ⅱ clinical trial: lower than the MTD group; The Phase II clinical trial included two groups. The dose of UC-MSCs received in each group patients will be determined based on the phase I results. One of the two groups subjects received the MTD obtained in phase I, and the other group subjects received a dose lower than the MTD. Each subject in the Phase II clinical trial received three dose of stem cell therapies after enrollment.The second therapy is 7 days after the first therapy, and the third therapy is 7 days after the second therapy.	Biological: Device: Phase II lower than the MTD in Phase I; This group subjects received a dose lower than the MTD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of serious adverse events	The incidence of serious adverse events (SAEs, such as recurrent bleeding, progressive stroke, brain death, respiratory failure, renal failure, circulatory failure, secondary epilepsy, sepsis, deep vein thrombosis, etc.) and treatment-related adverse events (TEAEs, such as fever or allergies after intravenous infusion of human umbilical cord mesenchymal stem cells(UC-MSCs)) occurring within 6 months of receiving UC-MSCs therapy.	Up to 6 months post-transplantation
Hematoma volume	Volume of intracerebral hemorrhage measured in cubic centimeters (cm³) as determined by quantitative analysis of head computed tomography scans.	Baseline and 7 days, 2 weeks, 1 month, 6 months post-transplantation for phase I; Baseline and 7 days, 2 weeks, 3 weeks, 1 month, 6 months post-transplantation for phase Ⅱ.
Peri-hematomal edema volume	Volume of edema surrounding the hematoma measured in cubic centimeters (cm³) as determined by quantitative analysis of head magnetic resonance imaging scans.	Baseline and 7 days, 2 weeks, 1 month, 6 months post-transplantation for phase I; Baseline and 7 days, 2 weeks, 3 weeks, 1 month, 6 months post-transplantation for phase Ⅱ.
National Institutes of Health Stroke Scale (NIHSS) score	The NIHSS is a neurological examination scale that provides a quantitative measure of stroke-related neurologic deficit. Scores range from 0 to 42 points, with higher scores indicating more severe neurological impairment.	Baseline and 7 days, 2 weeks, 3 weeks, 1 month, 3 months, 6 months post-transplantation for phase Ⅱ.
The modified Rankin Scale (mRS) score	The mRS measures the degree of disability or dependence in daily activities among individuals who have suffered a stroke. Scores range from 0 (no symptoms) to 6 (death), with higher scores indicating greater disability.	Baseline and 7 days, 2 weeks, 3 weeks, 1 month, 3 months, 6 months post-transplantation for phase Ⅱ.
Barthel Index scale score	The Barthel Index assesses functional independence in activities of daily living across 10 items. Total scores range from 0 to 100, with higher scores indicating greater independence in activities of daily living.	Baseline and 7 days, 2 weeks, 3 weeks, 1 month, 3 months, 6 months post-transplantation for phase Ⅱ.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events	The incidence of all non-serious adverse events occurring from infusion date through end of follow-up, including stress ulcers, pneumonia, injection site infections, and fever.	Up to 6 months post-transplantation
Pulmonary Embolism	Binary assessment (present/absent) of pulmonary embolism based on chest computed tomography with contrast enhancement.	Baseline and 7 days, 2 weeks, 1 month, 6 months post-transplantation for phase I; Baseline and 3 weeks, 6 months post-transplantation for phase Ⅱ.
Electrocardiogram ST Segment Deviation	Measurement of ST segment elevation or depression in millimeters from baseline. ST elevation ≥1mm in two or more contiguous leads or ST depression ≥0.5mm will be classified as abnormal.	Baseline and 1 day, 2 days, 7 days, 2 weeks, 3 weeks, 1 month, 3 months, 6 months post-transplantation for phase I.; Baseline and 7 days, 2 weeks, 3 weeks, 1 month, 6 months post-transplantation for phase Ⅱ.
Electrocardiogram Pathological Q Waves	Assessment for presence of pathological Q waves, defined as Q waves ≥40ms in duration or ≥25% of the height of the following R wave in at least two contiguous leads.	Baseline and 1 day, 2 days, 7 days, 2 weeks, 3 weeks, 1 month, 3 months, 6 months post-transplantation for phase I.; Baseline and 7 days, 2 weeks, 3 weeks, 1 month, 6 months post-transplantation for phase Ⅱ.
Electrocardiogram QTc Prolongation	Measurement of corrected QT interval in milliseconds. QTc intervals >450ms in males or >460ms in females will be classified as prolonged, indicating abnormal ventricular repolarization.	Baseline and 1 day, 2 days, 7 days, 2 weeks, 3 weeks, 1 month, 3 months, 6 months post-transplantation for phase I.; Baseline and 7 days, 2 weeks, 3 weeks, 1 month, 6 months post-transplantation for phase Ⅱ.
Electrocardiogram Arrhythmia Assessment	Identification and quantification of cardiac arrhythmias including atrial fibrillation, atrial flutter, ventricular tachycardia, ventricular fibrillation, and heart blocks. Results will be reported as presence or absence of each arrhythmia type.	Baseline and 1 day, 2 days, 7 days, 2 weeks, 3 weeks, 1 month, 3 months, 6 months post-transplantation for phase I.; Baseline and 7 days, 2 weeks, 3 weeks, 1 month, 6 months post-transplantation for phase Ⅱ.
Mini-Mental State Examination (MMSE) Score	The MMSE is a 30-point questionnaire used to measure cognitive impairment. Scores range from 0 to 30, with higher scores indicating better cognitive function.	Baseline and 7 days, 2 weeks, 3 weeks, 1 month, 3 months, 6 months post-transplantation for phase Ⅱ.
Montreal Cognitive Assessment (MoCA) Score	The MoCA is a cognitive screening test designed to detect mild cognitive impairment. Scores range from 0 to 30, with higher scores indicating better cognitive function.	Baseline and 7 days, 2 weeks, 3 weeks, 1 month, 3 months, 6 months post-transplantation for phase Ⅱ.
Hamilton Anxiety Scale (HAMA) Score	The HAMA is a 14-item scale that measures the severity of anxiety symptoms. Scores range from 0 to 56, with higher scores indicating more severe anxiety.	Baseline and 7 days, 2 weeks, 3 weeks, 1 month, 3 months, 6 months post-transplantation for phase Ⅱ.
Hamilton Depression Scale (HAMD) Score	The HAMD is a 17-item scale that measures the severity of depression symptoms. Scores range from 0 to 52, with higher scores indicating more severe depression.	Baseline and 7 days, 2 weeks, 3 weeks, 1 month, 3 months, 6 months post-transplantation for phase Ⅱ.
Serum Tumor Necrosis Factor-Alpha (TNF-alpha) Level	Concentration of TNF-alpha in pg/mL measured in serum samples.	Baseline and 7 days, 2 weeks, 1 month, 6 months post-transplantation for phase I.; Baseline and 7 days, 2 weeks, 3 weeks, 1 month, 6 months post-transplantation for phase Ⅱ.
Serum Interleukin-1 Beta (IL-1beta) Level	Concentration of IL-1beta in pg/mL measured in serum samples.	Baseline and 7 days, 2 weeks, 1 month, 6 months post-transplantation for phase I.; Baseline and 7 days, 2 weeks, 3 weeks, 1 month, 6 months post-transplantation for phase Ⅱ.
Serum Interleukin-2 Receptor (IL-2R) Level	Concentration of IL-2R in pg/mL measured in serum samples.	Baseline and 7 days, 2 weeks, 1 month, 6 months post-transplantation for phase I.; Baseline and 7 days, 2 weeks, 3 weeks, 1 month, 6 months post-transplantation for phase Ⅱ.
Serum Interleukin-6 (IL-6) Level	Concentration of IL-6 in pg/mL measured in serum samples.	Baseline and 7 days, 2 weeks, 1 month, 6 months post-transplantation for phase I.; Baseline and 7 days, 2 weeks, 3 weeks, 1 month, 6 months post-transplantation for phase Ⅱ.
Serum Interleukin-8 (IL-8) Level	Concentration of IL-8 in pg/mL measured in serum samples.	Baseline and 7 days, 2 weeks, 1 month, 6 months post-transplantation for phase I.; Baseline and 7 days, 2 weeks, 3 weeks, 1 month, 6 months post-transplantation for phase Ⅱ.
Serum Interleukin-10 (IL-10) Level	Concentration of IL-10 in pg/mL measured in serum samples.	Baseline and 7 days, 2 weeks, 1 month, 6 months post-transplantation for phase I.; Baseline and 7 days, 2 weeks, 3 weeks, 1 month, 6 months post-transplantation for phase Ⅱ.
Hemoglobin Level	Concentration of hemoglobin in blood measured in grams per deciliter (g/dL).	Baseline and 7 days, 2 weeks, 1 month, 6 months post-transplantation for phase I; Baseline and 7 days, 2 weeks, 3 weeks, 1 month, 6 months post-transplantation for phase Ⅱ.
White Blood Cell Count	Number of white blood cells per microliter (cells/μL) of blood.	Baseline and 7 days, 2 weeks, 1 month, 6 months post-transplantation for phase I; Baseline and 7 days, 2 weeks, 3 weeks, 1 month, 6 months post-transplantation for phase Ⅱ.
Platelet Count	Number of platelets per microliter (cells/μL) of blood.	Baseline and 7 days, 2 weeks, 1 month, 6 months post-transplantation for phase I; Baseline and 7 days, 2 weeks, 3 weeks, 1 month, 6 months post-transplantation for phase Ⅱ.
Alanine Aminotransferase (ALT) Level	Concentration of ALT enzyme in international units per liter (IU/L) as a measure of liver function.	Baseline and 7 days, 2 weeks, 1 month, 6 months post-transplantation for phase I; Baseline and 7 days, 2 weeks, 3 weeks, 1 month, 6 months post-transplantation for phase Ⅱ.
Aspartate Aminotransferase (AST) Level	Concentration of AST enzyme in international units per liter (IU/L) as a measure of liver function.	Baseline and 7 days, 2 weeks, 1 month, 6 months post-transplantation for phase I; Baseline and 7 days, 2 weeks, 3 weeks, 1 month, 6 months post-transplantation for phase Ⅱ.
Blood Urea Nitrogen (BUN) Level	Concentration of BUN in milligrams per deciliter (mg/dL) as a measure of kidney function.	Baseline and 7 days, 2 weeks, 1 month, 6 months post-transplantation for phase I; Baseline and 7 days, 2 weeks, 3 weeks, 1 month, 6 months post-transplantation for phase Ⅱ.
Serum Creatinine Level	Concentration of creatinine in milligrams per deciliter (mg/dL) as a measure of kidney function.	Baseline and 7 days, 2 weeks, 1 month, 6 months post-transplantation for phase I; Baseline and 7 days, 2 weeks, 3 weeks, 1 month, 6 months post-transplantation for phase Ⅱ.
Urine Protein Level	Concentration of protein in urine measured in milligrams per deciliter (mg/dL).	Baseline and 7 days, 2 weeks, 1 month, 6 months post-transplantation for phase I; Baseline and 7 days, 2 weeks, 3 weeks, 1 month, 6 months post-transplantation for phase Ⅱ.
Urine Red Blood Cell Count	Number of red blood cells per high-power field (HPF) in urine microscopy.	Baseline and 7 days, 2 weeks, 1 month, 6 months post-transplantation for phase I; Baseline and 7 days, 2 weeks, 3 weeks, 1 month, 6 months post-transplantation for phase Ⅱ.
Fecal Occult Blood Test	Qualitative assessment of occult blood in stool (positive or negative).	Baseline and 7 days, 2 weeks, 1 month, 6 months post-transplantation for phase I; Baseline and 7 days, 2 weeks, 3 weeks, 1 month, 6 months post-transplantation for phase Ⅱ.
Serum Sodium Level	Concentration of sodium in serum measured in millimoles per liter (mmol/L).	Baseline and 7 days, 2 weeks, 1 month, 6 months post-transplantation for phase I; Baseline and 7 days, 2 weeks, 3 weeks, 1 month, 6 months post-transplantation for phase Ⅱ.
Serum Potassium Level	Concentration of potassium in serum measured in millimoles per liter (mmol/L).	Baseline and 7 days, 2 weeks, 1 month, 6 months post-transplantation for phase I; Baseline and 7 days, 2 weeks, 3 weeks, 1 month, 6 months post-transplantation for phase Ⅱ.
Prothrombin Time (PT)	Time required for plasma to clot after addition of tissue factor, measured in seconds.	Baseline and 7 days, 2 weeks, 1 month, 6 months post-transplantation for phase I; Baseline and 7 days, 2 weeks, 3 weeks, 1 month, 6 months post-transplantation for phase Ⅱ.
Activated Partial Thromboplastin Time (aPTT)	Time required for plasma to clot after activation of intrinsic pathway, measured in seconds.	Time required for plasma to clot after activation of intrinsic pathway, measured in seconds.
Total Cholesterol Level	Concentration of total cholesterol in serum measured in milligrams per deciliter (mg/dL).	Baseline and 7 days, 2 weeks, 1 month, 6 months post-transplantation for phase I; Baseline and 7 days, 2 weeks, 3 weeks, 1 month, 6 months post-transplantation for phase Ⅱ.
High-Density Lipoprotein (HDL) Cholesterol Level	Concentration of HDL cholesterol in serum measured in milligrams per deciliter (mg/dL).	Baseline and 7 days, 2 weeks, 1 month, 6 months post-transplantation for phase I; Baseline and 7 days, 2 weeks, 3 weeks, 1 month, 6 months post-transplantation for phase Ⅱ.
Low-Density Lipoprotein (LDL) Cholesterol Level	Concentration of LDL cholesterol in serum measured in milligrams per deciliter (mg/dL).	Baseline and 7 days, 2 weeks, 1 month, 6 months post-transplantation for phase I; Baseline and 7 days, 2 weeks, 3 weeks, 1 month, 6 months post-transplantation for phase Ⅱ.
Fasting Blood Glucose Level	Concentration of glucose in blood after overnight fasting, measured in milligrams per deciliter (mg/dL).	Baseline and 7 days, 2 weeks, 1 month, 6 months post-transplantation for phase I; Baseline and 7 days, 2 weeks, 3 weeks, 1 month, 6 months post-transplantation for phase Ⅱ.
CD4+ T Lymphocyte Count	Number of CD4+ T lymphocytes per microliter (cells/μL) of blood as a measure of immune function.	Baseline and 7 days, 2 weeks, 1 month, 6 months post-transplantation for phase I; Baseline and 7 days, 2 weeks, 3 weeks, 1 month, 6 months post-transplantation for phase Ⅱ.
CD8+ T Lymphocyte Count	Number of CD8+ T lymphocytes per microliter (cells/μL) of blood as a measure of immune function.	Baseline and 7 days, 2 weeks, 1 month, 6 months post-transplantation for phase I; Baseline and 7 days, 2 weeks, 3 weeks, 1 month, 6 months post-transplantation for phase Ⅱ.
CD4+/CD8+ Ratio	Ratio of CD4+ to CD8+ T lymphocytes as a measure of immune system balance.	Baseline and 7 days, 2 weeks, 1 month, 6 months post-transplantation for phase I; Baseline and 7 days, 2 weeks, 3 weeks, 1 month, 6 months post-transplantation for phase Ⅱ.
High-Sensitivity C-Reactive Protein (hs-CRP) Level	Concentration of hs-CRP in milligrams per liter (mg/L) as a measure of inflammation.	Baseline and 7 days, 2 weeks, 1 month, 6 months post-transplantation for phase I; Baseline and 7 days, 2 weeks, 3 weeks, 1 month, 6 months post-transplantation for phase Ⅱ.
Middle Cerebral Artery Blood Flow Velocity	Mean blood flow velocity in the middle cerebral artery measured in centimeters per second (cm/s) using transcranial Doppler ultrasonography.	Baseline and 7 days, 2 weeks, 1 month, 6 months post-transplantation for phase I; Baseline and 6 months post-transplantation for phase Ⅱ.
Pulsatility Index	Ratio of the difference between peak systolic and end-diastolic velocities to the mean velocity in cerebral arteries as measured by transcranial Doppler ultrasonography. Higher values indicate increased vascular resistance.	Baseline and 7 days, 2 weeks, 1 month, 6 months post-transplantation for phase I; Baseline and 6 months post-transplantation for phase Ⅱ.
Carotid Artery Stenosis Percentage	Degree of carotid artery stenosis expressed as percentage reduction in vessel diameter as measured by computed tomography angiography.	Baseline and 7 days, 2 weeks, 1 month, 6 months post-transplantation for phase I; Baseline and 6 months post-transplantation for phase Ⅱ.
Electroencephalogram Delta Wave Activity	Quantitative measurement of delta wave (0.5-4 Hz) power in microvolts squared (μV²). Increased focal delta activity outside of sleep states indicates abnormal cerebral function.	Baseline and 7 days, 2 weeks, 1 month, 6 months post-transplantation for phase I; Baseline and 3 weeks , 6 months post-transplantation for phase Ⅱ.
Electroencephalogram Epileptiform Discharges	Quantification of epileptiform discharges (spikes, sharp waves, spike-and-wave complexes) per hour of recording. Presence of ≥1 discharge per hour will be classified as abnormal.	Baseline and 7 days, 2 weeks, 1 month, 6 months post-transplantation for phase I; Baseline and 3 weeks , 6 months post-transplantation for phase Ⅱ.
Electroencephalogram Background Rhythm Analysis	Assessment of background rhythm frequency in Hertz (Hz) and amplitude in microvolts (μV). Normal adult awake posterior dominant rhythm is 8-13 Hz (alpha rhythm). Slowing below 8 Hz will be classified as abnormal.	Baseline and 7 days, 2 weeks, 1 month, 6 months post-transplantation for phase I; Baseline and 3 weeks , 6 months post-transplantation for phase Ⅱ.
Corticospinal Tract Integrity	Tractography-based assessment of corticospinal tract integrity expressed as percentage of fibers preserved compared to the unaffected hemisphere. Values range from 0% to 100%, with lower percentages indicating greater tract damage.	Baseline and 7 days, 2 weeks, 1 month, 6 months post-transplantation for phase I; Baseline and 6 months post-transplantation for phase Ⅱ.
Electroencephalogram Hemispheric Asymmetry	Baseline and 7 days, 2 weeks, 1 month, 6 months post-transplantation for phase I; Baseline and 3 weeks , 6 months post-transplantation for phase Ⅱ.	Quantitative comparison of power spectral density between homologous regions of both cerebral hemispheres. Asymmetry of >50% in any frequency band will be classified as abnormal.

Collaborators and Investigators

• Sponsor: Tang Zhouping
• Collaborators: Wuhan Hamilton Biotechnology Co., Ltd
• Investigators: Principal Investigator: Zhouping Tang, M.D., Tongji Hospital

Publications and helpful links

General Publications

• Hanley DF, Thompson RE, Rosenblum M, Yenokyan G, Lane K, McBee N, Mayo SW, Bistran-Hall AJ, Gandhi D, Mould WA, Ullman N, Ali H, Carhuapoma JR, Kase CS, Lees KR, Dawson J, Wilson A, Betz JF, Sugar EA, Hao Y, Avadhani R, Caron JL, Harrigan MR, Carlson AP, Bulters D, LeDoux D, Huang J, Cobb C, Gupta G, Kitagawa R, Chicoine MR, Patel H, Dodd R, Camarata PJ, Wolfe S, Stadnik A, Money PL, Mitchell P, Sarabia R, Harnof S, Barzo P, Unterberg A, Teitelbaum JS, Wang W, Anderson CS, Mendelow AD, Gregson B, Janis S, Vespa P, Ziai W, Zuccarello M, Awad IA; MISTIE III Investigators. Efficacy and safety of minimally invasive surgery with thrombolysis in intracerebral haemorrhage evacuation (MISTIE III): a randomised, controlled, open-label, blinded endpoint phase 3 trial. Lancet. 2019 Mar 9;393(10175):1021-1032. doi: 10.1016/S0140-6736(19)30195-3. Epub 2019 Feb 7. Erratum In: Lancet. 2019 Apr 20;393(10181):1596. doi: 10.1016/S0140-6736(19)30859-1.
• Moise KJ Jr. Umbilical cord stem cells. Obstet Gynecol. 2005 Dec;106(6):1393-407. doi: 10.1097/01.AOG.0000188388.84901.e4.
• Li T, Xia M, Gao Y, Chen Y, Xu Y. Human umbilical cord mesenchymal stem cells: an overview of their potential in cell-based therapy. Expert Opin Biol Ther. 2015;15(9):1293-306. doi: 10.1517/14712598.2015.1051528. Epub 2015 Jun 12.
• Tsang KS, Ng CPS, Zhu XL, Wong GKC, Lu G, Ahuja AT, Wong KSL, Ng HK, Poon WS. Phase I/II randomized controlled trial of autologous bone marrow-derived mesenchymal stem cell therapy for chronic stroke. World J Stem Cells. 2017 Aug 26;9(8):133-143. doi: 10.4252/wjsc.v9.i8.133.
• Chang Z, Mao G, Sun L, Ao Q, Gu Y, Liu Y. Cell therapy for cerebral hemorrhage: Five year follow-up report. Exp Ther Med. 2016 Dec;12(6):3535-3540. doi: 10.3892/etm.2016.3811. Epub 2016 Oct 18.
• Hu Y, Liu N, Zhang P, Pan C, Zhang Y, Tang Y, Deng H, Aimaiti M, Zhang Y, Zhou H, Wu G, Tang Z. Preclinical Studies of Stem Cell Transplantation in Intracerebral Hemorrhage: a Systemic Review and Meta-Analysis. Mol Neurobiol. 2016 Oct;53(8):5269-77. doi: 10.1007/s12035-015-9441-6. Epub 2015 Sep 26.
• Gao L, Xu W, Li T, Chen J, Shao A, Yan F, Chen G. Stem Cell Therapy: A Promising Therapeutic Method for Intracerebral Hemorrhage. Cell Transplant. 2018 Dec;27(12):1809-1824. doi: 10.1177/0963689718773363. Epub 2018 Jun 5.
• Gong YH, Hao SL, Wang BC. Mesenchymal Stem Cells Transplantation in Intracerebral Hemorrhage: Application and Challenges. Front Cell Neurosci. 2021 Mar 24;15:653367. doi: 10.3389/fncel.2021.653367. eCollection 2021.
• Zhou JF, Xiong Y, Kang X, Pan Z, Zhu Q, Goldbrunner R, Stavrinou L, Lin S, Hu W, Zheng F, Stavrinou P. Application of stem cells and exosomes in the treatment of intracerebral hemorrhage: an update. Stem Cell Res Ther. 2022 Jun 28;13(1):281. doi: 10.1186/s13287-022-02965-2.
• Yang G, Fan X, Mazhar M, Yang S, Xu H, Dechsupa N, Wang L. Mesenchymal Stem Cell Application and Its Therapeutic Mechanisms in Intracerebral Hemorrhage. Front Cell Neurosci. 2022 Jun 13;16:898497. doi: 10.3389/fncel.2022.898497. eCollection 2022.
• Mishra VK, Shih HH, Parveen F, Lenzen D, Ito E, Chan TF, Ke LY. Identifying the Therapeutic Significance of Mesenchymal Stem Cells. Cells. 2020 May 6;9(5):1145. doi: 10.3390/cells9051145.
• Ding DC, Shyu WC, Lin SZ. Mesenchymal stem cells. Cell Transplant. 2011;20(1):5-14. doi: 10.3727/096368910X.
• Puy L, Parry-Jones AR, Sandset EC, Dowlatshahi D, Ziai W, Cordonnier C. Intracerebral haemorrhage. Nat Rev Dis Primers. 2023 Mar 16;9(1):14. doi: 10.1038/s41572-023-00424-7.

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2025
• Primary Completion (Estimated): February 28, 2027
• Study Completion (Estimated): July 31, 2027

Study Registration Dates

• First Submitted: November 3, 2023
• First Submitted That Met QC Criteria: March 2, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 2, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Inflammation; Intracerebral hemorrhage; Stem cell therapy; Human umbilical cord mesenchymal stem cells; Neural repair
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Intracranial Hemorrhages; Hemorrhage; Cerebral Hemorrhage
• Other Study ID Numbers: TJ-IRB202502088; ChiCTR2500095990 (Other Identifier: Chinese Clinical Trial Registry)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No