The Phase I/II Randomized, Prospective, Double-blinded, Sham-controlled Cross-over Study of Intravitreal Autologous Bone Marrow CD34+ Stem Cell Therapy for Retinal Vein Occlusion

玻璃体内自体骨髓 CD34 干细胞治疗视网膜静脉阻塞的 I/II 期随机、前瞻性、双盲、假手术对照交叉研究

• 批准号: 10163850
• 负责人: SUSANNA S PARK
• 金额: $ 61.12万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-06-15 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10163850
• 关键词: Acute; Address; Adverse event; Affect; Age-Years; Aspirate substance; Autologous; Blindness; Blood Circulation; Blood Vessels; Bone Marrow; Bone Marrow Aspiration; Bone Marrow Cells; Bone Marrow Involvement; Bone Marrow Transplantation; CD34 gene; California; Cardiomyopathies; Cell Therapy; Cells; Chronic; Clinical Trials; Cross-Over Studies; Data; Diabetic Retinopathy; Disease; Double-Blind Method; Elderly; Electroretinography; Enrollment; Ensure; Eye; Fluorescein Angiography; Fluorescence; Fundus photography; Goals; Human; Incidence; Injections; Ischemia; Leadership; Manuscripts; Masks; Medicine; Monitor; Morphology; Nature; Older Population; Ophthalmic examination and evaluation; Ophthalmologist; Ophthalmology; Optical Coherence Tomography; Outcome Measure; Perfusion; Phase; Phase I/II Clinical Trial; Placebos; Play; Principal Investigator; Protocols documentation; Publications; Randomized; Regenerative Medicine; Reporting; Research; Retina; Retinal Diseases; Retinal Vein Occlusion; Role; Safety; Sample Size; Severities; Source; Testing; TimeLine; Tissues; Universities; Vision; Visual Acuity; Writing; bone; bone cell; design; effective therapy; endothelial stem cell; improved; improved functioning; intravitreal injection; ischemic injury; novel; preclinical study; primary outcome; prospective; protective effect; recruit; regenerative; repaired; response; retina blood vessel structure; retina circulation disorder; retinal ischemia; retinal regeneration; safety and feasibility; secondary outcome; stem cell therapy; tissue regeneration; trend

Project Summary: The goal of this phase I/II prospective, randomized, sham-controlled, double-blinded clinical trial is to determine whether intravitreal autologous CD34+ cell therapy is safe, feasible and potentially beneficial in eyes with vision loss from retinal vein occlusion (RVO). RVO is a leading retinal vascular cause of vision loss in the elderly. CD34+ cells in human bone marrow are mobilized into the circulation in response to tissue ischemia for tissue revascularization and repair. Since local delivery of CD34+ cells benefits ischemic tissue, intravitreal delivery of CD34+ cells may benefit vision and retinal ischemia in eyes with RVO. A pilot clinical trial has shown no major safety or feasibility concerns using intravitreal autologous CD34+ bone marrow cells. In this expanded phase I/II study, 15 subjects (15 eyes) with persistent vision loss from RVO will be enrolled and follow for 2 years. Total study duration will be 60 months. This single- center study will be at the University of California Davis. The Coordinating Center will be Emmes Corporation. The Study Chair/Principal Investigator will be Dr. Susanna Park. The study will be conducted under an IND cleared from FDA. A Data and Safety Monitoring Committee will oversee the study. Subjects will be randomized at enrollment 2:1 to cell therapy or sham/deferred cell therapy. The cell therapy involves bone marrow aspiration, isolation of CD34+ cells from the aspirate under Good Manufacturing Practice conditions, and intravitreal injection of isolated CD34+ cells. Sham therapy involves sham bone marrow aspiration and intravitreal injection without penetrating the bone or eye. The subject, examining ophthalmologist and visual acuity examiner will remain masked to study treatment randomization till month six. Thereafter, the study will be unmasked and the sham-treated subjects will undergo bone marrow aspiration and cell therapy. A comprehensive eye examination with ETDRS best-corrected visual acuity, optical coherence tomography, auto- fluorescence, fundus photography, fluorescein angiography, microperimetry and electroretinography will be performed at baseline and serially. The primary outcome measures will be the incidence and severity of ocular and systemic adverse events associated with cell therapy and the number of CD34+ cells isolated for injection. The secondary outcome measures will be the changes in visual function, retinal perfusion and morphology following cell therapy. The long-term objective is to determine whether intravitreal autologous CD34+ cell therapy can minimize or reverse vision loss associated with retinal ischemia without compromising safety.

项目概要： 该 I/II 期临床试验的目标是前瞻性、随机、假对照、双盲 临床试验旨在确定玻璃体内自体CD34+细胞治疗是否安全、可行 对于因视网膜静脉阻塞 (RVO) 导致视力丧失的眼睛可能有益。 RVO 是一个 导致老年人视力丧失的主要视网膜血管原因。人骨髓中的 CD34+ 细胞 响应组织缺血而动员到循环中以进行组织血运重建和 维修。由于 CD34+ 细胞的局部递送有利于缺血组织，因此玻璃体内递送 CD34+ 细胞可能有益于 RVO 眼睛的视力和视网膜缺血。一项试点临床试验已 使用玻璃体内自体 CD34+ 骨髓没有显示出重大的安全性或可行性问题 细胞。在这项扩大的 I/II 期研究中，15 名受试者（15 只眼睛）患有持续性视力丧失， RVO 将注册并跟踪 2 年。总学习时间为60个月。这个单 中心研究将在加州大学戴维斯分校进行。协调中心将是 埃姆斯公司。研究主席/首席研究员将是 Susanna Park 博士。研究 将根据 FDA 批准的 IND 进行。数据和安全监测委员会将 监督研究。受试者将在入组时以 2:1 的比例随机分配至细胞疗法或 假手术/延迟细胞治疗。细胞疗法包括骨髓抽吸、分离 在良好生产规范条件下抽取的 CD34+ 细胞和玻璃体内的 CD34+ 细胞 注射分离的CD34+细胞。假治疗包括假骨髓抽吸和 玻璃体内注射，不穿透骨骼或眼睛。主题，审查 眼科医生和视力检查员将继续蒙面研究治疗 随机化直至第六个月。此后，该研究将被揭开，并接受假治疗 受试者将接受骨髓抽吸和细胞治疗。全面的眼光 使用 ETDRS 最佳矫正视力、光学相干断层扫描、自动 荧光、眼底照相、荧光素血管造影、显微视野检查和 将在基线时连续进行视网膜电图检查。主要结果指标 将是与细胞相关的眼部和全身不良事件的发生率和严重程度 治疗和分离用于注射的 CD34+ 细胞的数量。次要结果指标 细胞治疗后视觉功能、视网膜灌注和形态的变化。 长期目标是确定玻璃体内自体 CD34+ 细胞疗法是否可以 在不影响安全性的情况下，最大限度地减少或逆转与视网膜缺血相关的视力丧失。