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: 9765377
• 负责人: ARSHED A QUYYUMI
• 金额: $ 75.17万
• 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 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9765377
• 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; Colony-Stimulating Factors; Data; Dose; Endothelium; Exercise; Experimental Models; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Hematopoietic; Homing; Impairment; Injections; Intermittent Claudication; Ischemia; Leukocytes; Limb structure; Measures; Modality; Modeling; Morbidity - disease rate; Mus; Natural regeneration; Pain; Patients; Peripheral; Peripheral arterial disease; Pharmacology; Phase; Physical Function; Placebos; Plasmids; Population; Protocols documentation; Quality of life; Randomized; Safety; Site; Stem cells; Symptoms; Testing; Therapeutic; Time; Ulcer; Walking; base; claudication; density; improved; improved functioning; indexing; macrophage; monocyte; neovascularization; novel strategies; paracrine; phase III trial; placebo group; reduce symptoms; repaired; sargramostim; secondary outcome; smoking cessation; subcutaneous; tissue repair; treadmill; trend

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 anklebrachial index.

外周动脉疾病（PAD）困扰着大约15%的55岁以上的美国人口。后 在最初的无症状期，PAD患者通常会出现间歇性跛行， 最终发展为严重的肢体缺血和持续的疼痛、溃疡和截肢。虽然 运动、戒烟、抗血小板治疗、西洛他唑、他汀类药物和血运重建可以减轻 症状，几乎三分之一的PAD患者继续患有间歇性跛行， 严重影响了他们的生活质量。干细胞和祖细胞（PC）治疗，促进 新血管生成和再血管化是PAD的新兴治疗方式。粒细胞-巨噬细胞 集落刺激因子（GM-CSF）刺激造血和其它PC从骨中的动员 骨髓我们已经在PAD患者的I期剂量递增试验和IIA期试验中证明了 和跛行，GM-CSF动员PC进入循环，是安全的，并导致改善， 跛行。 我们现在建议研究骨髓PC动员的影响， 在患有动脉粥样硬化性PAD和步行的患者中以3个月的间隔皮下施用GM-CSF 损伤我们的假设是GM-CSF将改善PAD患者的步行距离和生活质量 和行走障碍我们将在6分钟步行测试和步行距离上测量改善情况。 与安慰剂相比，两次GM-CSF给药后，间隔三个月。作为次要 结果，我们还将调查与单次相比，两次是否有进一步的改善 给予GM-CSF，以及是否伴随着生活质量参数和踝臂功能的改善。 指数.