Allogeneic Mononuclear Umbilical Cord Blood Systemic Infusions for Adult Patients With Severe Acute Contusion Spinal Cord Injury: Phase I Safety Study and Phase IIa Primary Efficiency Study
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Neurological Deficit Change [ASIA scale]
研究概览
简要总结
Study evaluates the safety and primary efficiency of systemic (i.v.) allogeneic human umbilical cord blood mononuclear cell infusions in patients with severe acute contusion spinal cord injury (ASIA A/B). 20 patients were included. Half of patients received cell therapy in addition to standard therapy, while the other half received standard therapy only.
详细描述
Present study was prospective randomized open-label clinical study, Phases I/IIa. Randomization was performed using envelope method (50 envelopes including Cell Therapy and Standard Therapy, 25 of each).
20 patients with severe scute contusion spinal cord injury (cervical, thoracic and lumbar cone segments) were included into the study. Patients were divided into 2 groups: pilot group (n = 10) obtaining standard conservative therapy and 4 i.v. infusions of Human Allogeneic Umbilical Cord Blood Mononuclear Cells (hUCBMCs) (~ 300 M in 100 mL) and control group (n = 10) obtaining standard conservative therapy only. Cell Therapy was initiated in patients within 3 days after SCI episode after primary surgical decompression and/or stabilization was performed. Patients inclusion decision depended on meeting the inclusion/exclusion criteria and informed consent signed.
hUCBMC samples were prepared in the specialized laboratory and transported to the hospital immediately within 2 hours. Cells infusions were performed following 3 tests for biological compatibility and potential intolerance for each patient.
All four infusion were performed during in-hospital treatment. Observational period reached 1 year after SCI. All included patients were examined daily during in-hospital treatment following 4 times within observational period (1 year).
All adverse events and potential complications were analyzed within 1 year after SCI using CTCAE v5.0 classification.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •acute spinal cord injury (first 3 days after trauma)
- •contusion type of SCI (MRI-confirmed)
- •Russian citizenship
- •Informed consent understood and signed by the patient
排除标准
- •systolic arterial pressure (APsyst) > 185 mmHg OR diastolic AP (APdia) > 105 mmHg OR indications for aggressive AP lowering using i.v. therapy
- •myocardial infarction within 3 months prior to SCI
- •glucose level < 3.5 mM/L or > 21 mM/L
- •organic CNS pathology
- •acute internal organs diseases requiring surgical treatment
- •autoimmune diseases
- •serious surgical treatment or severe trauma within 3 months prior to SCI
- •pregnancy or breast feeding
- •acute infections including tuberculosis, syphilis, HIV, hepatitis B and C etc.
- •severe acute and chronic hematological diseases
- •rare patient's blood group parameters preventing adequate hUCBMCs sample selection (e.g. Kell+, A2B group, rare phenotype etc.)
- •any benign or oncological tumors (if not fully treated prior to SCI)
- •inability to participate in key examination following clinic discharge
- •any psychiatric diseases preventing patient from informed consent OR treatment plan understanding
- •confirmed hypersensitivity and/or allergy to any component of the studied biological compound
- •inability to accomplish present study protocol
研究组 & 干预措施
Pilot group
10 patients with acute severe contusion spinal cord injury (ASIA A/B) included into the group. Patients meeting inclusion/exclusion criteria underwent primary surgical treatment (decompression and stabilization) received hUCBMC infusions weekly (4 infusions overall) in addition to standard therapy during in-hospital treatment. After the discharge patients were examined for 4 times. Observation period was 1 year.
干预措施: Human Allogeneic Umbilical Cord Blood Mononuclear Cells (hUCBMCs) systemic (i.v.) infusions (Biological)
Control group
10 patients with acute severe contusion spinal cord injury (ASIA A/B) included into the group. Patients meeting inclusion/exclusion criteria underwent primary surgical treatment (decompression and stabilization) received standard therapy during in-hospital treatment. After the discharge patients were examined for 4 times. Observation period was 1 year.
结局指标
主要结局
Neurological Deficit Change [ASIA scale]
时间窗: Change from Baseline at 1 year after SCI
Dynamics of neurological deficit level within 1 year after SCI was analyzed using ASIA clinical scale: ASIA A - total motor and sensory impairment; ASIA B - total motor impairment and partial sensory impairment below SCI level or pelvic sensitivity preserved; ASIA C - incomplete motor (at least half of key muscle strength less than 3 points) and sensory impairment; ASIA D - incomplete motor (at least half of key muscle strength more than 3 points) and sensory impairment; ASIA E - normal. Neurological deficit level was compared between pilot and control groups.
Quality of Life [FIM scale]
时间窗: 1 year after SCI
Quality of life level was assessed within 1 year after SCI using FIM (functional impairment) scale. FIM scale evaluates 5 groups of parameters including motor functions and self-service, mobility, motion level, pelvic functions and intellectual functions (e.g. communication and social activity). Each group includes several parameters assessed using point system (maximum 7 points for each parameter). A total sum of points is counted and compared between pilot and control groups.
Incidence of Treatment-Emergent Adverse Events [Safety]
时间窗: 1 year
All potential adverse events were analyzed during the first year after SCI. All adverse events (AEs) were classified using CTCAE v5.0 classification system in each of 10 patients of pilot group. Severity of AEs: Grade 1 - mild; asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2 - moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental ADL; Grade 3 - severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated, disabling, limiting self care ADL; Grade 4 - life-threatening consequences; urgent intervention indicated; Grade 5 - death related to AE. Relationship to the investigated therapy method: Degree 1 - unrelated; Degree 2 - possibly related; Degree 3 - probably related; Degree 4 - definitely related.
次要结局
- Motor Deficit Change [Muscle Strength](Change from Baseline at 1 year after SCI)
- Independent Verticalization Ability(1 year after SCI)
- Lower Extremities Spasticity Level [Modified Asworth scale](1 year after SCI)
- Feeling of Bladder Filling(1 year after SCI)
- Spinal Cord Conductivity [Electrophysiological assessment](1 year after SCI)
- Urinary Inconsistence(1 year after SCI)
研究者
Vladimir A. Smirnov
MD
Sklifosovsky Institute of Emergency Care