Chronic lower limb ischemia develops earlier and more frequently in patients with type 2 diabetes mellitus. Diabetes remains the main cause of lower-extremity non-traumatic amputations. Current medical treatment, based on antiplatelet therapy and statins, has demonstrated deficient improvement of the disease. In recent years, research has shown that it is possible to improve tissue perfusion through therapeutic angiogenesis. Both in animal models and humans, it has been shown that cell therapy can induce therapeutic angiogenesis, making mesenchymal stromal cell-based therapy one of the most promising therapeutic alternatives. The aim of this study is to evaluate the feasibility, safety, and efficacy of cell therapy based on mesenchymal stromal cells derived from adipose tissue intramuscular administration to patients with type 2 diabetes mellitus with critical limb ischemia and without possibility of revascularization. A multicenter, randomized double-blind, placebo-controlled trial has been designed. Ninety eligible patients will be randomly assigned at a ratio 1:1:1 to one of the following: control group (n = 30), low-cell dose treatment group (n = 30), and high-cell dose treatment group (n = 30). Treatment will be administered in a single-dose way and patients will be followed for 12 months. Primary outcome (safety) will be evaluated by measuring the rate of adverse events within the study period. Secondary outcomes (efficacy) will be measured by assessing clinical, analytical, and imaging-test parameters. Tertiary outcome (quality of life) will be evaluated with SF-12 and VascuQol-6 scales. Chronic lower limb ischemia has limited therapeutic options and constitutes a public health problem in both developed and underdeveloped countries. Given that the current treatment is not established in daily clinical practice, it is essential to provide evidence-based data that allow taking a step forward in its clinical development. Also, the multidisciplinary coordination exercise needed to develop this clinical trial protocol will undoubtfully be useful to conduct academic clinical trials in the field of cell therapy in the near future. ClinicalTrials.gov NCT04466007 . Registered on January 07, 2020. All items from the World Health Organization Trial Registration Data Set are included within the body of the protocol.

中文翻译：

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肌内注射同种异体脂肪组织衍生的和扩增的间充质基质细胞在无法进行血运重建的糖尿病患者中的有效性和安全性：随机对照双盲 II 期临床试验（NOMA 试验）的研究方案

慢性下肢缺血在 2 型糖尿病患者中发生得更早、更频繁。糖尿病仍然是下肢非创伤性截肢的主要原因。目前基于抗血小板治疗和他汀类药物的医学治疗已证明对该疾病的改善不足。近年来，研究表明可以通过治疗性血管生成来改善组织灌注。在动物模型和人类中，已经表明细胞疗法可以诱导治疗性血管生成，使基于间充质基质细胞的疗法成为最有前途的治疗选择之一。本研究的目的是评估可行性、安全性、和基于来自脂肪组织的间充质基质细胞的细胞疗法对患有严重肢体缺血且无血运重建可能性的 2 型糖尿病患者进行肌肉注射给药的效果。设计了一项多中心、随机、双盲、安慰剂对照试验。90 名符合条件的患者将按 1:1:1 的比例随机分配到以下其中一项：对照组（n = 30）、低细胞剂量治疗组（n = 30）和高细胞剂量治疗组（n = 30）。治疗将以单剂量方式给药，患者将被随访 12 个月。主要结果（安全性）将通过测量研究期内不良事件的发生率来评估。次要结果（功效）将通过评估临床、分析和成像测试参数来衡量。三级结果（生活质量）将使用 SF-12 和 VascuQol-6 量表进行评估。慢性下肢缺血的治疗选择有限，在发达国家和不发达国家都构成公共卫生问题。鉴于目前的治疗方法尚未在日常临床实践中建立，因此必须提供循证数据，以便在其临床开发中向前迈出一步。此外，开发该临床试验方案所需的多学科协调工作无疑将有助于在不久的将来进行细胞治疗领域的学术临床试验。ClinicalTrials.gov NCT04466007。2020 年 1 月 7 日注册。来自世界卫生组织试验注册数据集的所有项目都包含在协议正文中。