Granulocyte-Macrophage Colony Stimulated Factor (GM-CSF) in Peripheral Arterial Disease

粒细胞-巨噬细胞集落刺激因子 (GM-CSF) 在外周动脉疾病中的应用

• 批准号: 9385242
• 负责人: ARSHED A QUYYUMI
• 金额: $ 77.51万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-15 至 2018-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9385242
• 关键词: Address; Age-Years; Alternative Therapies; Amputation; Ankle; Arteries; Autologous; Blood Circulation; Blood Vessels; Blood capillaries; Bone Marrow; Cell Count; Cell Therapy; Cells; Cilostazol; Clinical Trials; Data; Dose; Exercise; Experimental Models; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Hematopoietic; Homing; Impairment; Injection of therapeutic agent; Intermittent Claudication; Ischemia; Leukocytes; Limb structure; Measures; Modality; Modeling; Morbidity - disease rate; Mus; Natural regeneration; Pain; Patients; Performance; Peripheral; Peripheral arterial disease; Pharmacology; Phase; Physical Function; Placebos; Plasmids; Population; Protocols documentation; Quality of life; Randomized; Safety; Site; Stem cells; Subcutaneous Injections; Symptoms; Testing; Therapeutic; Time; Ulcer; Walking; base; capillary; claudication; density; exercise capacity; improved; improved functioning; indexing; macrophage; monocyte; neovascularization; novel strategies; paracrine; phase III trial; reduce symptoms; repaired; sargramostim; secondary outcome; smoking cessation; subcutaneous; tissue repair; treadmill; trend

Project Summary Peripheral arterial disease (PAD) afflicts approximately 15% of the U.S. population over 55 years of age. After an initial asymptomatic period, patients with PAD typically develop intermittent claudication, which may eventually progress to critical limb ischemia and unrelenting pain, ulceration and amputation. Although exercise, smoking cessation, anti-platelet therapy, cilostazol, statins and revascularization can mitigate symptoms, almost a third of the patients with PAD continue to suffer from intermittent claudication that profoundly impairs their quality of life. Stem cell and progenitor cell (PC) therapy that promotes neoangiogenesis and revascularization is an emerging treatment modality in PAD. Granulocyte -macrophage colony stimulating factor (GM-CSF) stimulates mobilization of hematopoietic and other PCs from the bone marrow. We have demonstrated in a Phase I dose-escalation trial and in a Phase IIA trial in patients with PAD and claudication that GM-CSF mobilizes PCs into the circulation, is safe and results in improvement in claudication. We now propose to investigate the effects of mobilization of bone marrow PCs with two successive administrations of subcutaneous GM-CSF at 3 month intervals in patients with atherosclerotic PAD and walking impairment. Our hypothesis is that GM-CSF will improve walking distance and quality of life in patients with PAD and walking impairment. We will measure improvement in the 6-minute walk test and in walking distance on the treadmill and after two administrations of GM-CSF, three months apart compared to placebo. As secondary outcomes, we will also investigate whether there is further improvement with two compared to single administration of GM-CSF, and whether there is concomitant improvement in quality of life parameters and ankle- brachial index.

项目摘要 周围动脉疾病（PAD）折磨了55岁以上美国人口的15％。后 初始无症状时期，PAD患者通常会发育间歇性lau不平，这可能 最终发展为关键的肢体缺血和不屈不挠的疼痛，溃疡和截肢。虽然 运动，戒烟，抗血小板疗法，西洛舍唑，他汀类药物和血运重建可以减轻 症状，几乎三分之一的患有PAD的患者继续患有间歇性lau不平 严重损害他们的生活质量。促进的干细胞和祖细胞（PC）治疗 新血管生成和血运重建是PAD中的一种新兴治疗方式。粒细胞 - 巨噬细胞 菌落刺激因子（GM-CSF）刺激造血和其他PC的动员 骨髓。我们已经在I期剂量升级试验和PAD患者的IIA期试验中证明了 GM-CSF将PC动员到循环系统中，并且可以改善 laurauration。 现在，我们建议研究骨髓PC的动员的影响 在患有动脉粥样硬化垫和步行的患者的3个月间隔内，皮下GM-CSF的施用 损害。我们的假设是GM-CSF将改善PAD患者的步行距离和生活质量 和行走障碍。我们将测量6分钟步行测试的改进以及步行距离 跑步机和两个GM-CSF的管理后，与安慰剂相比，相距三个月。作为次要 结果，我们还将调查与单个相比，两个 GM-CSF的给药，以及生活质量参数和踝关节的同时提高 臂指数。