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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要大约 15% 的 55 岁以上美国人口患有外周动脉疾病 (PAD)。后在最初的无症状期，PAD 患者通常会出现间歇性跛行，这可能最终进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缓解症状，近三分之一的 PAD 患者继续患有间歇性跛行，严重损害了他们的生活质量。干细胞和祖细胞 (PC) 疗法可促进新生血管生成和血运重建是 PAD 的一种新兴治疗方式。粒细胞-巨噬细胞集落刺激因子 (GM-CSF) 刺激造血细胞和其他骨细胞的动员骨髓。我们已经在 PAD 患者的 I 期剂量递增试验和 IIA 期试验中证明了这一点 GM-CSF 动员 PC 进入循环，是安全的，并能改善跛行。我们现在建议研究连续两次动员骨髓 PC 的效果动脉粥样硬化 PAD 和步行患者每隔 3 个月皮下注射 GM-CSF 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。我们将衡量 6 分钟步行测试和步行距离的改善情况跑步机上和两次 GM-CSF 给药后，与安慰剂相比，间隔三个月。作为次要结果，我们还将调查与单个相比，两个是否有进一步的改进 GM-CSF 的施用，以及生活质量参数和踝关节功能是否随之改善肱指数。