Transdermal H2S Sensing Device for Monitoring Peripheral Artery Disease

用于监测外周动脉疾病的透皮 H2S 传感装置

• 批准号: 10546652
• 负责人: Reza Shekarriz
• 金额: $ 50万
• 依托单位: EXHALIX, LLC
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-06 至 2024-08-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10546652
• 关键词: Address; Adoption; Affect; Age; Age Distribution; American; Amputation; Analgesics; Angiography; Ankle; Atherosclerosis; Attention; Biological Availability; Biological Markers; Biometry; Blood Vessels; Blood flow; Blood specimen; Businesses; Cardiovascular Physiology; Cardiovascular system; Cell Line; Clinical; Clinical Research; Clinical Trials; Collaborations; Current Procedural Terminology Codes; Detection; Development; Devices; Diabetes Mellitus; Diagnosis; Disease; Endothelial Cells; Endothelium; Engineering; Environment; Evaluation; Female; Functional disorder; Funding; Gases; Government; Hand; Health; Health Care Costs; Health Personnel; High Density Lipoproteins; Hydrogen Sulfide; Individual; Infarction; Ischemia; Kidney; Lead; Limb Salvage; Limb structure; Low-Density Lipoproteins; Lower Extremity; Measurement; Measures; Medical Device; Methodology; Microvascular Dysfunction; Monitor; Multi-Institutional Clinical Trial; Muscle; National Heart, Lung, and Blood Institute; New Mexico; Non-Insulin-Dependent Diabetes Mellitus; Operative Surgical Procedures; Organ failure; Outcome; Pain; Participant; Pathologic; Patient Care; Patients; Performance; Perfusion; Peripheral arterial disease; Phase; Physiology; Plasma; Population; Privatization; Production; Protocols documentation; Quality of life; Reading; Recovery; Research; Research Personnel; Resources; Risk; Severities; Signal Transduction; Site; Skin; Small Business Innovation Research Grant; Study Subject; Technology; Testing; Time; Toes; Transcutaneous Oximetry; Type 2 diabetic; Universities; Vascular Diseases; Vascular calcification; Vasodilator Agents; atherosclerosis risk; authority; cardiovascular risk factor; care costs; chronic wound; clinical diagnosis; cohort; commercialization; cost; cost effectiveness; detector; diabetic; diabetic patient; diagnostic platform; diagnostic tool; economic value; effective intervention; effective therapy; endothelial dysfunction; experience; healing; high risk; human subject; improved; indexing; innovation; male; medical schools; meetings; monitoring device; myocardial damage; noninvasive diagnosis; patient population; point of care; portability; pre-clinical; preclinical study; prevent; primary outcome; prognostication; programs; prototype; renal damage; research clinical testing; revascularization surgery; sensor; socioeconomics; tool; user-friendly; wound; wound healing; wound treatment

Project Summary/Abstract Peripheral artery disease (PAD) and small vessel disease (SVD) are the consequences of damage to the endothelial cells that line all vessels, leading to inadequate skin perfusion, end-organ failure, and limb damage. This damage is prevalent in the diabetic patient population where nearly 50% suffers from PAD and SVD. Numerous studies describe the difficulties of diagnosing vascular disease in diabetic patients, either due to limited access to the cost-prohibitive Transcutaneous Oximetry (TcPO2), lack of accuracy in limb blood flow evaluation using Ankle Brachial Index (ABI), or the high risk of kidney damage with the use of invasive angiography. The proposed effort addresses this unmet need by offering a simple, inexpensive, and effective device ideal for widespread clinical use to detect and follow the course of PAD and SVD. The expected socioeconomic impacts of clinical adoption of the proposed technology include improvement in patient quality of life by delaying or preventing the development of debilitating disease and a decrease in patient care costs. Our diagnostic system utilizes hydrogen sulfide (H2S), a newly described endothelium-derived vasodilator, that decreases with the onset of endothelial damage and dysfunction. Importantly, normal production of H2S is essential for endothelial function, for improving recovery from muscle ischemia, and to mitigate damage from myocardial and kidney infarction. The technology, Transdermal Arterial Gasotransmitter Sensor (TAGS™), employs an innovative gas-phase detector which noninvasively measures trace levels of H2S emitted from the skin as a measure of vascular health in the skin. During a NHLBI-funded Phase II SBIR research effort, TAGS™ measurements were carried out in human subjects to assess local vascular and microvascular health in healthy individuals, asymptomatic T2D patients, and symptomatic T2D patients with limb-threatening wounds undergoing lower-extremity revascularization surgery. It was found that TAGS™ signals correlate inversely with atherosclerotic and cardiovascular risk score, ASCVD, and with HgbA1C and LDL/HDL ratio (i.e., the biomarkers of diabetes). The results also reveal that PAD in diabetes decreases the bioavailability of H2S in the lower extremity (leg) skin of patients with diabetes so that TAGS™ readings can assess the severity of skin microvascular disease. The proposed CRP pre-clinical study is intended to engage more clinicians to test the TAGS™ methodology against other measures of vascular health and to increase the size of each cohort to provide appropriate power for statistical evaluation. Successful completion of the CRP effort by meeting our Specific Aims is expected to lead to Phase IIB clinical studies.

项目概要/摘要 外周动脉疾病 (PAD) 和小血管疾病 (SVD) 是内皮细胞损伤的后果 它们遍布所有血管，导致皮肤灌注不足、终末器官衰竭和肢体损伤。这种伤害很普遍 在糖尿病患者群体中，近 50% 患有 PAD 和 SVD。许多研究描述了困难 诊断糖尿病患者血管疾病的方法，要么是由于成本高昂的经皮血管的获取有限 血氧饱和度 (TcPO2)、使用踝臂指数 (ABI) 评估肢体血流缺乏准确性或肾病风险高 使用侵入性血管造影术造成的损伤。拟议的工作通过提供一个简单的、 廉价且有效的设备，非常适合临床广泛使用，用于检测和追踪 PAD 和 SVD 的病程。这 临床采用拟议技术的预期社会经济影响包括提高患者质量 通过延迟或预防衰弱性疾病的发展以及降低患者护理费用来改善生命。我们的 诊断系统利用硫化氢（H2S），这是一种新描述的内皮衍生血管舒张剂，随着 内皮损伤和功能障碍的发生。重要的是，H2S 的正常产生对于内皮细胞至关重要 功能，改善肌肉缺血的恢复，并减轻心肌和肾梗塞的损害。 该技术名为透皮动脉气体发射传感器 (TAGS™)，采用创新的气相检测器， 无创地测量从皮肤散发的痕量 H2S 水平，作为皮肤血管健康的衡量标准。期间 NHLBI 资助的第二阶段 SBIR 研究工作，在人类受试者中进行了 TAGS™ 测量，以评估局部 健康个体、无症状 T2D 患者和有症状 T2D 患者的血管和微血管健康 接受下肢血运重建手术的威胁肢体的伤口。研究发现 TAGS™ 信号相关 与动脉粥样硬化和心血管风险评分、ASCVD 以及 HgbA1C 和 LDL/HDL 比率（即 糖尿病的生物标志物）。结果还表明，糖尿病患者的 PAD 会降低下丘脑中 H2S 的生物利用度。 糖尿病患者的四肢（腿部）皮肤，以便 TAGS™ 读数可以评估皮肤微血管疾病的严重程度。 拟议的 CRP 临床前研究旨在吸引更多临床医生针对其他方法测试 TAGS™ 方法 血管健康的测量并增加每个队列的规模，为统计评估提供适当的能力。 通过满足我们的具体目标，成功完成 CRP 工作预计将导致 IIB 期临床研究。