Stem Cell Therapy for Intracerebral Hemorrhage

NCT06862388 | Not Yet Recruiting Phase 1 DMC

• 2 other identifiers: TJ-IRB202502088ChiCTR2500095990
• Study Type: interventional
• Target: 39
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Intracerebral Hemorrhage; Mesenchymal Stem Cell

Keywords

Intracerebral hemorrhage; Human umbilical cord mesenchymal stem cells; Stem cell therapy; Inflammation; Neural repair

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (46)

• Incidence of adverse events

  Up to 6 months post-transplantation

• Pulmonary Embolism

  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

  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

  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

  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.

Study Arms (3)

PhaseⅠclinical trial: 3+3 dose-escalation design

EXPERIMENTAL

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; Biological: Device: Phase Ⅰ Dose Level 2; Biological: Device: Phase Ⅰ Dose Level 3

Phase Ⅱ clinical trial: MTD group

EXPERIMENTAL

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

Phase Ⅱ clinical trial: lower than the MTD group

EXPERIMENTAL

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

Interventions

Device: Phase Ⅰ Dose Level 1 BIOLOGICAL

Patients in the first dose level will receive a cell dose of 1×10\^6 cells/kg.

PhaseⅠclinical trial: 3+3 dose-escalation design

Device: Phase Ⅰ Dose Level 2 BIOLOGICAL

Patients in the second dose level will receive a cell dose of 2×10\^6 cells/kg.

PhaseⅠclinical trial: 3+3 dose-escalation design

Device: Phase Ⅰ Dose Level 3 BIOLOGICAL

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.

PhaseⅠclinical trial: 3+3 dose-escalation design

Device: Phase II MTD in Phase I BIOLOGICAL

This group subjects received the MTD obtained in phase I.

Phase Ⅱ clinical trial: MTD group

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

This group subjects received a dose lower than the MTD

Phase Ⅱ clinical trial: lower than the MTD group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-65 years old, gender is not limited.
• Clinically confirmed intracerebral hemorrhage during the subacute period (3 days-10 days after onset).
• 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)).
• 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.
• National Institutes of Health Stroke Scale score (NIHSS) ≥5 and ≤20.
• Pre-onset modified Ranking Scale score (mRS) ≤1.
• Glasgow Coma Score (GCS) ≥9 points and ≥3 points on a single item.
• Good compliance, signed informed consent by the person and/or legal guardian and able to receive follow-up visits at the specified time.

You may not qualify if:

• Brain midline deviation \>10 mm or brain hernia formation.
• Patients who have undergone or intend to undergo surgical treatment to remove hematoma.
• Secondary intracerebral hemorrhage caused by traumatic brain injury, arteriovenous malformation, intracranial aneurysm, coagulation disorders, hemorrhagic transformation after cerebral infarction, or tumors.
• 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.
• 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.
• Pregnant or lactating women.
• History of stroke disease with sequelae in the last 1 year, NIHSS score ≥ 6.
• Subarachnoid hemorrhage, primary ventricular hemorrhage, pharmacological hemorrhagic stroke.
• 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.
• Those who are participating in other clinical trials.
• Previous history of epilepsy or current use of antiepileptic drugs.
• Unable to accept all laboratory tests and imaging tests designed by the program due to metal implants or pacemakers in the body.
• Inability to complete the follow-up program as required.
• Patients or their legal guardians are unwilling to sign the written informed consent.

Sponsors & Collaborators

• Tang Zhouping: lead
• Wuhan Hamilton Biotechnology Co., Ltd: collaborator

Related Publications (13)

• Moise KJ Jr. Umbilical cord stem cells. Obstet Gynecol. 2005 Dec;106(6):1393-407. doi: 10.1097/01.AOG.0000188388.84901.e4.

  PMID: 16319269 BACKGROUND

• 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.

  PMID: 26067213 BACKGROUND

• 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.

  PMID: 28928910 BACKGROUND

• 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.

  PMID: 28101148 BACKGROUND

• 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.

  PMID: 26409481 BACKGROUND

• 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.

  PMID: 29871521 BACKGROUND

• 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.

  PMID: 33841103 BACKGROUND

• 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.

  PMID: 35765072 BACKGROUND

• 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.

  PMID: 35769327 BACKGROUND

• 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.

  PMID: 32384763 BACKGROUND

• Ding DC, Shyu WC, Lin SZ. Mesenchymal stem cells. Cell Transplant. 2011;20(1):5-14. doi: 10.3727/096368910X.

  PMID: 21396235 BACKGROUND

• 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.

  PMID: 30739747 BACKGROUND

• 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.

  PMID: 36928219 BACKGROUND

MeSH Terms

Conditions

Cerebral Hemorrhage; Inflammation

Interventions

Clinical Trials, Phase I as Topic

Condition Hierarchy (Ancestors)

Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Clinical Trials as Topic; Clinical Studies as Topic; Epidemiologic Study Characteristics; Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Study Officials

• Zhouping Tang, M.D.

  Tongji Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhouping Tang, M.D.

CONTACT

+86-18071423962; ddjtzp@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Model Details: 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.

Study Record Dates

• First Submitted: November 3, 2023
• First Posted: March 6, 2025
• Study Start: March 1, 2025
• Primary Completion (Estimated): February 28, 2027
• Study Completion (Estimated): July 31, 2027
• Last Updated: March 6, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share