Clinical trial NCT06862388: Stem Cell Therapy for Intracerebral Hemorrhage
Official title: Clinical Research on Umbilical Cord Mesenchymal Stem Cells Therapy for Patients with Subacute Intracerebral Hemorrhage
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Intracerebral Hemorrhage
Mesenchymal Stem Cell
Keywords: Intracerebral hemorrhage
Human umbilical cord mesenchymal stem cells
Stem cell therapy
Inflammation
Neural repair
Lead sponsor: Tongji Hospital
Sponsor class: OTHER
Collaborators: name: Wuhan Hamilton Biotechnology Co., Ltd
First posted: 2025-03-06
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: The clinical trial was divided into phase I and Phase II. The Phase I clinical trial is a Sequential design, and the Phase II clinical trial is a Parallel design.
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of serious adverse events
timeFrame: Up to 6 months post-transplantation
measure: Hematoma volume
timeFrame: 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.
measure: Peri-hematomal edema volume
timeFrame: 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.
measure: National Institutes of Health Stroke Scale (NIHSS) score
timeFrame: Baseline and 7 days, 2 weeks, 3 weeks, 1 month, 3 months, 6 months post-transplantation for phase Ⅱ.
measure: The modified Rankin Scale (mRS) score
timeFrame: Baseline and 7 days, 2 weeks, 3 weeks, 1 month, 3 months, 6 months post-transplantation for phase Ⅱ.
measure: Barthel Index scale score
timeFrame: Baseline and 7 days, 2 weeks, 3 weeks, 1 month, 3 months, 6 months post-transplantation for phase Ⅱ.
Secondary outcomes:
measure: Incidence of adverse events
timeFrame: Up to 6 months post-transplantation
measure: Pulmonary Embolism
timeFrame: 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.
measure: Electrocardiogram ST Segment Deviation
timeFrame: 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.
measure: Electrocardiogram Pathological Q Waves
timeFrame: 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.
measure: Electrocardiogram QTc Prolongation
timeFrame: 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.
measure: Electrocardiogram Arrhythmia Assessment
timeFrame: 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.
measure: Mini-Mental State Examination (MMSE) Score
timeFrame: Baseline and 7 days, 2 weeks, 3 weeks, 1 month, 3 months, 6 months post-transplantation for phase Ⅱ.
measure: Montreal Cognitive Assessment (MoCA) Score
timeFrame: Baseline and 7 days, 2 weeks, 3 weeks, 1 month, 3 months, 6 months post-transplantation for phase Ⅱ.
measure: Hamilton Anxiety Scale (HAMA) Score
timeFrame: Baseline and 7 days, 2 weeks, 3 weeks, 1 month, 3 months, 6 months post-transplantation for phase Ⅱ.
measure: Hamilton Depression Scale (HAMD) Score
timeFrame: Baseline and 7 days, 2 weeks, 3 weeks, 1 month, 3 months, 6 months post-transplantation for phase Ⅱ.
measure: Serum Tumor Necrosis Factor-Alpha (TNF-alpha) Level
timeFrame: 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.
measure: Serum Interleukin-1 Beta (IL-1beta) Level
timeFrame: 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.
measure: Serum Interleukin-2 Receptor (IL-2R) Level
timeFrame: 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.
measure: Serum Interleukin-6 (IL-6) Level
timeFrame: 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.
measure: Serum Interleukin-8 (IL-8) Level
timeFrame: 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.
measure: Serum Interleukin-10 (IL-10) Level
timeFrame: 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.
measure: Hemoglobin Level
timeFrame: 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.
measure: White Blood Cell Count
timeFrame: 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.
measure: Platelet Count
timeFrame: 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.
measure: Alanine Aminotransferase (ALT) Level
timeFrame: 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.
measure: Aspartate Aminotransferase (AST) Level
timeFrame: 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.
measure: Blood Urea Nitrogen (BUN) Level
timeFrame: 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.
measure: Serum Creatinine Level
timeFrame: 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.
measure: Urine Protein Level
timeFrame: 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.
measure: Urine Red Blood Cell Count
timeFrame: 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.
measure: Fecal Occult Blood Test
timeFrame: 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.
measure: Serum Sodium Level
timeFrame: 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.
measure: Serum Potassium Level
timeFrame: 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.
measure: Prothrombin Time (PT)
timeFrame: 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.
measure: Activated Partial Thromboplastin Time (aPTT)
timeFrame: Time required for plasma to clot after activation of intrinsic pathway, measured in seconds.
measure: Total Cholesterol Level
timeFrame: 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.
measure: High-Density Lipoprotein (HDL) Cholesterol Level
timeFrame: 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.
measure: Low-Density Lipoprotein (LDL) Cholesterol Level
timeFrame: 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.
measure: Fasting Blood Glucose Level
timeFrame: 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.
measure: CD4+ T Lymphocyte Count
timeFrame: 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.
measure: CD8+ T Lymphocyte Count
timeFrame: 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.
measure: CD4+/CD8+ Ratio
timeFrame: 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.
measure: High-Sensitivity C-Reactive Protein (hs-CRP) Level
timeFrame: 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.
measure: Middle Cerebral Artery Blood Flow Velocity
timeFrame: Baseline and 7 days, 2 weeks, 1 month, 6 months post-transplantation for phase I; Baseline and 6 months post-transplantation for phase Ⅱ.
measure: Pulsatility Index
timeFrame: Baseline and 7 days, 2 weeks, 1 month, 6 months post-transplantation for phase I; Baseline and 6 months post-transplantation for phase Ⅱ.
measure: Carotid Artery Stenosis Percentage
timeFrame: Baseline and 7 days, 2 weeks, 1 month, 6 months post-transplantation for phase I; Baseline and 6 months post-transplantation for phase Ⅱ.
measure: Electroencephalogram Delta Wave Activity
timeFrame: 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.
measure: Electroencephalogram Epileptiform Discharges
timeFrame: 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.
measure: Electroencephalogram Background Rhythm Analysis
timeFrame: 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.
measure: Corticospinal Tract Integrity
timeFrame: Baseline and 7 days, 2 weeks, 1 month, 6 months post-transplantation for phase I; Baseline and 6 months post-transplantation for phase Ⅱ.
measure: Electroencephalogram Hemispheric Asymmetry
timeFrame: 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.
Other outcomes:
Locations:
Study officials:
affiliation: Tongji Hospital
name: Zhouping Tang, M.D.
role: PRINCIPAL_INVESTIGATOR
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