Autologous Bone Marrow Aspirate Concentrate for the Treatment of Osteonecrosis of the Femoral Head

自体骨髓抽吸浓缩液治疗股骨头坏死

• 批准号: 10658324
• 负责人: STUART B GOODMAN
• 金额: $ 77.91万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-10 至 2028-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10658324
• 关键词: Arthritis; Autologous; Biological; Biology; Biometry; Blood Vessels; Bone Marrow Aspiration; Bone necrosis; Case Series; Cell Therapy; Cells; Cessation of life; Characteristics; Circulation; Classification; Clinical; Clinical Trials; Clinical/Radiologic; Consensus; Cytometry; Data Coordinating Center; Data Set; Diagnosis; Disease; Early Diagnosis; Early treatment; Elements; Equipoise; Failure; Frequencies; Goals; Grant; Harvest; Healthcare; Heterogeneity; Hip Joint; Hip region structure; Individual; Infrastructure; International; Joints; Laboratories; Lesion; Life; Literature; Location; Marrow; Methodology; Modeling; Multi-Institutional Clinical Trial; Multicenter Studies; Multicenter Trials; Musculoskeletal Diseases; National Institute of Arthritis, and Musculoskeletal, and Skin Diseases; Operative Surgical Procedures; Outcome; Pain; Pathogenesis; Patient-Focused Outcomes; Patients; Pelvis; Persons; Pharmacologic Substance; Phenotype; Procedures; Publishing; Radiology Specialty; Randomized; Randomized Controlled Clinical Trials; Randomized, Controlled Trials; Reporting; Research Design; Risk Factors; Sampling; Societies; Specimen; Staging; Standardization; Techniques; Testing; Time; Total Hip Replacement; United States; Variant; bone; care burden; clinical practice; common treatment; design; effective intervention; efficacy evaluation; end stage disease; evidence base; femur head; hip replacement arthroplasty; improved; interest; joint destruction; loss of function; member; operation; preservation; prevent; prospective; radiologist; recruit; stem cells; subchondral bone; success; tissue regeneration; tissue repair; treatment arm; Arthritis; Autologous; Biological; Biology; Biometry; Blood Vessels; Bone Marrow Aspiration; Bone necrosis; Case Series; Cell Therapy; Cells; Cessation of life; Characteristics; Circulation; Classification; Clinical; Clinical Trials; Clinical/Radiologic; Consensus; Cytometry; Data Coordinating Center; Data Set; Diagnosis; Disease; Early Diagnosis; Early treatment; Elements; Equipoise; Failure; Frequencies; Goals; Grant; Harvest; Healthcare; Heterogeneity; Hip Joint; Hip region structure; Individual; Infrastructure; International; Joints; Laboratories; Lesion; Life; Literature; Location; Marrow; Methodology; Modeling; Multi-Institutional Clinical Trial; Multicenter Studies; Multicenter Trials; Musculoskeletal Diseases; National Institute of Arthritis, and Musculoskeletal, and Skin Diseases; Operative Surgical Procedures; Outcome; Pain; Pathogenesis; Patient-Focused Outcomes; Patients; Pelvis; Persons; Pharmacologic Substance; Phenotype; Procedures; Publishing; Radiology Specialty; Randomized; Randomized Controlled Clinical Trials; Randomized, Controlled Trials; Reporting; Research Design; Risk Factors; Sampling; Societies; Specimen; Staging; Standardization; Techniques; Testing; Time; Total Hip Replacement; United States; Variant; bone; care burden; clinical practice; common treatment; design; effective intervention; efficacy evaluation; end stage disease; evidence base; femur head; hip replacement arthroplasty; improved; interest; joint destruction; loss of function; member; operation; preservation; prevent; prospective; radiologist; recruit; stem cells; subchondral bone; success; tissue regeneration; tissue repair; treatment arm

Abstract/Project Summary Osteonecrosis of the femoral head (ONFH) is characterized by disrupted circulation within the bony compartment, leading to death of bone and marrow cells. It is associated with progressive pain, bony collapse, and joint degeneration within months to several years. Over 10 million people are afflicted worldwide. Most patients are diagnosed in their mid-30s, during their peak working years. The pathogenesis and treatment of this disease are controversial. If diagnosed early, the goal is to preserve the native hip joint. Total hip replacement is reserved for painful end-stage disease. Core decompression (CD) is the most common treatment in the early stages of ONFH and creates a drill tract into the lesion. However, the clinical outcome of CD is variable. There is increasing interest in using bone marrow aspirate concentrate (BMAC) to augment CD. Yet, studies have been limited to small case series, different disease stages, multiple risk factors, variable surgical techniques, or otherwise have lacked rigor. A randomized controlled trial (RCT) is needed to obtain a more definitive answer regarding the efficacy of BMAC with CD for early-stage ONFH. The overall goal of our multicenter clinical trial (U01) is to test the following hypotheses: “Patients who have early-stage ONFH undergoing CD augmented with autogenous BMAC will have better clinical and radiological outcomes than CD alone.” This RCT will also define specific patient characteristics that determine the long-term outcomes of these procedures. The Co-PIs are world-renowned experts, who are academic and clinical leaders in osteonecrosis. A team of highly recognized clinicians, who have expertise in the treatment of osteonecrosis from 12 centers in the United States have been recruited. For standardization, we will utilize a centralized radiologist, a central bone biology laboratory, and a center for data management and biostatistical analysis. Our specific aims are: Specific Aim 1 (SA1). To determine if CD with autogenous BMAC results in better outcomes than CD alone for the treatment of early-stage (pre-collapse) ARCO Stage I and II ONFH. Specific Aim 2 (SA2). SA 2A. To determine the cellular phenotype of the patients’ bone marrow aspirates, as assessed by Mass Cytometry by Time of Flight (CyTOF). SA 2B. To build a multivariate model classifying patients who have satisfactory and unsatisfactory clinical and/or radiological outcomes based on the combined mass cytometry cell frequency and functional feature dataset. In summary, we have planned this multicenter trial with our NIAMS-sponsored project team (R34 AR073505) and assembled a team of experts in the diagnosis and treatment of ONFH. The trial will benefit from existing studies and infrastructure by our group. We will determine if ON patients benefit from autogenous BMAC to augment CD, and investigate the biological mechanisms underlying improvements in outcome.

摘要/项目摘要 股骨头（ONFH）的骨坏死的特征是奖金中的圆圈中断 车厢，导致骨骼和骨髓细胞死亡。它与进行性疼痛，邦迪崩溃有关 和几个月到几年的联合变性。全世界有超过1000万人遭受折磨。最多 在工作年龄高峰期，患者在30年代中期被诊断出。的发病机理和治疗 这种疾病是有争议的。如果早点被诊断出，目标是保留本地髋关节。总臀部 替换保留用于痛苦的终疾病。核心减压（CD）是最常见的 在ONFH的早期阶段进行治疗，并在病变中产生钻头。但是， CD是可变的。对使用骨髓抽吸物浓缩物（BMAC）增强CD的兴趣越来越大。 然而，研究仅限于小病例系列，不同的疾病阶段，多个危险因素，可变。 手术技术，或其他缺乏严格性。 需要进行随机对照试验（RCT），以获得有关效率的更确定的答案 BMAC与CD进行早期阶段。我们多中心临床试验（U01）的总体目标是测试 以下假设：“患有自动源的CD的早期阶段的患者 BMAC将比单独使用CD具有更好的临床和放射学结局。 决定这些程序的长期结果的患者特征。 Co-Pis是世界知名的专家，他们是骨坏死的学术和临床领导者。一个团队 备受认可的临床医生，他们在12个中心的骨坏死治疗方面具有专业知识 美国已被招募。为了进行标准化，我们将使用集中放射科医生，一个中央骨头 生物学实验室，以及数据管理和生物统计分析中心。 我们的具体目的是： 特定目标1（SA1）。确定与自体BMAC的CD是否相比仅与CD相比会产生更好的结果 为了治疗早期（爆发前）ARCO阶段I和II阶段。 特定目标2（SA2）。 SA 2A。确定患者骨髓攻击的细胞表型，因为 通过飞行时间（CytoF）通过质量细胞仪评估。 SA 2B。构建多元模型分类 基于合并的临床和/或放射性结果的患者 质量细胞仪细胞频率和功能特征数据集。 总而言之，我们已经计划了Niams赞助的项目团队（R34 AR073505）进行了这项多中心试验。 并组建了一个专家团队的ONFH诊断和治疗。审判将从现有 我们小组的研究和基础设施。我们将确定患者是否受益于自体BMAC 增强CD，并研究结果改善的生物学机制。