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）折磨着大约15%的55岁以上的美国人口。后