Stem Cell Therapy for Intracerebral Hemorrhage

Tang Zhouping

Status and phase: Not yet enrolling; Phase 2; Phase 1

Conditions: Intracerebral Hemorrhage; Mesenchymal Stem Cell

Treatments: Biological: Device: Phase Ⅰ Dose Level 1; Biological: Device: Phase Ⅰ Dose Level 3; Biological: Device: Phase II lower than the MTD in Phase I; Biological: Device: Phase II MTD in Phase I; Biological: Device: Phase Ⅰ Dose Level 2

Study type: Interventional

Funder types: Other

Identifiers

NCT06862388

ChiCTR2500095990 (Other Identifier)

TJ-IRB202502088

Details and patient eligibility

About

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.

Full 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.

Enrollment: 39 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

---

39 participants in 3 patient groups

PhaseⅠclinical trial: 3+3 dose-escalation design

Experimental group

Description:

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.

Treatment:

Biological: Device: Phase Ⅰ Dose Level 2

Biological: Device: Phase Ⅰ Dose Level 3

Biological: Device: Phase Ⅰ Dose Level 1

Phase Ⅱ clinical trial: MTD group

Experimental group

Description:

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.

Treatment:

Biological: Device: Phase II MTD in Phase I

Phase Ⅱ clinical trial: lower than the MTD group

Experimental group

Description:

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.

Treatment:

Biological: Device: Phase II lower than the MTD in Phase I