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

基本信息

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
项目类别：
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

项目摘要

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.

项目摘要/摘要外围动脉疾病（PAD）和小血管疾病（SVD）是对内皮细胞损害的后果所有容器，导致皮肤灌注不足，末端器官衰竭和肢体损伤。这种伤害很普遍在糖尿病患者人群中，近50％的患者患有PAD和SVD。许多研究描述了困难糖尿病患者的诊断血管疾病，要么是由于经验有限血氧仪（TCPO2），使用踝臂指数（ABI）或肾脏高风险的肢体流动评估缺乏准确性使用侵入性血管造影的损害。提出的工作通过提供简单的，廉价且有效的设备非常适合宽度临床使用，以检测和遵循PAD和SVD的过程。这拟议技术的临床采用的预期社会经济影响包括改善患者质量通过延迟或防止衰弱的疾病发展和患者护理费用降低来实现生活。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的血管扩张剂，随着降低内皮损伤和功能障碍的发作。重要的是，H2S的正常产生对于内皮必不可少功能，可改善肌肉缺血的恢复，并减轻心肌和肾脏梗塞的损害。该技术，透皮动脉递质传感器（TAGS™），员工是创新的气相检测器非侵入性测量从皮肤发出的痕量水平，以衡量皮肤血管健康。在 NHLBI资助的II期SBIR研究工作，Tags™测量在人类受试者中进行了评估以评估本地健康个体，无症状T2D患者和有症状的T2D患者的血管健康和微血管健康危及肢体的伤口正在接受较低的血管血运重建手术。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比率相反（即，糖尿病的生物标志物）。结果还表明，糖尿病的垫降低了较低的H2S的生物利用度糖尿病患者的肢体（腿）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临床前研究旨在让更多的临床医生与其他临床医生测试Tags™方法论血管健康的度量并增加每个队列的规模，以提供适当的统计评估功能。通过实现我们的具体目标，可以成功完成CRP的工作，这将导致IIB期临床研究。