Development of a novel technology for the determination of a physiologic phenotype in patients with Systemic Lupus Erythematosus

在这一应用中，我们建议对一种用于测量系统的新型医疗设备进行初步验证 红斑狼疮(SLE)疾病活动性。系统性红斑狼疮是一种累及多器官的复杂炎症性疾病。 系统。用于跟踪炎症的现有评估工具和实验室测试不能可靠地反映 患者报告了症状。此外，这些生物标志物无法预测耀斑状态的开始。 研究表明，管理良好的狼疮患者积累的器官损害较少，并表现出 随着时间的推移，结果会有所改善。临床上对反映疾病的可靠生物标记物的需求尚未得到满足。 活动促进治疗一种特定的SLE疾病的活动表型和严重程度。这项措施 将有助于指导免疫抑制治疗的充分性或表明需要治疗其他症状。 对这种终点的定期监测有可能预测活动中的耀斑，这将使早期， 采取先发制人的干预措施，改善患者预后。AlgemetRx Inc.是从儿童国家医院剥离出来的 医院(CNH)开发该提案中使用的新技术并将其商业化。这个设备是 一种新型的红外无创无创神经选择性电刺激 瞳孔测量法激活特定类型的感觉神经纤维，并允许客观量化 感觉神经纤维活性的表征。具体地说，这项技术衡量了SLE的影响- 感觉神经纤维活性的相关炎症。生成的SLE指数可以进行比较 在个人内部以及个人之间随着时间的推移而采取的措施之间。在这项提案中，我们计划 在开发一种易于实施的、非侵入性的、客观的 系统性红斑狼疮疾病活动性的生理测量。为了实现这一目标，我们提出了以下目标和方法： 目的：建立SLE指数作为SLE疾病活动性的客观指标的初步验证。 我们将招募20名转诊至CNH多学科狼疮诊所的SLE患者，并评估他们的狼疮 每月疾病活动持续6至12个月。在每次就诊期间，评估患者的SLE疾病 活动将使用SLEDAI-2K临床评估工具和我们的设备进行。我们将建立 通过评估敏感性、特异性和安全性，初步验证SLE指数作为疾病活动性的衡量标准 SLE指数的可靠性。在针对SLEDAI-2K进行初步验证之后，我们计划接下来进行第二阶段 提案将进一步验证该指数，并将促进一项更大规模的研究，以量化治疗的影响 在SLE患者中。第二阶段还将告知我们需要额外的数据来支持最初的FDA Clearance是监测SLE疾病活动的一种工具。在此开发的应用程序 该方案将能够及早检测病情，优化SLE表型和严重程度特定的治疗 为了最大限度地提高疾病反应，促进早期治疗干预，将器官损害的风险降至最低， 并有可能被用作开发新的SLE疗法的临床试验终点。

In this application, we propose the initial validation of a novel medical device for the measurement of systemic lupus erythematosus (SLE) disease activity. SLE is a complex inflammatory disease involving many organ systems. The existing assessment tools and laboratory tests used to track inflammation do not reliably reflect patient reported symptoms. Furthermore, these biomarkers are unable to predict the onset of a flare state. Studies have shown that patients with well managed lupus accumulate less organ damage and demonstrate improved outcomes over time. There is an unmet clinical need for reliable biomarkers that reflect disease activity to facilitate the treatment of a specific SLE disease activity phenotype and severity. This measure would help to guide the adequacy of immunosuppressive therapy or indicate a need to treat other symptoms. Regular monitoring of such an endpoint has the potential to predict a flare in activity, which would enable early, preemptive interventions and improve patient outcomes. AlgometRx Inc., was spun out of Children’s National Hospital (CNH) to develop and commercialize the novel technology being used in this proposal. This device is a novel integration of non-invasive and innocuous neuroselective electrical stimulation with infrared pupillometry to activate specific sensory nerve fiber types and allows for an objective quantified characterization of sensory nerve fiber activity. Specifically, this technology measures the impact of SLE- associated inflammation on sensory nerve fiber activity. The resulting SLE Index enables comparisons between measures over time within an individual as well as between individuals. In this proposal, we plan to expand upon our preliminary data in the development of an easily implemented, non-invasive and objective physiologic measure of SLE disease activity. To accomplish this, we propose the following aim and approach: Aim: Establish the initial validation of the SLE Index as an objective measure of SLE disease activity. We will enroll 20 SLE patients referred to the Multidisciplinary Lupus Clinic at CNH and assess their lupus disease activity each month for 6 to 12 months. During each clinic visit, assessment of a patient’s SLE disease activity will be performed using the SLEDAI-2K clinical assessment tool and our device. We will establish the initial validation of the SLE Index as a measure of disease activity by assessing sensitivity, specificity, and reliability of the SLE Index. After this initial validation against the SLEDAI-2K, we plan to follow with a Phase II proposal that will further validate the index and will facilitate a larger study to quantify the impact of treatments in patients with SLE. The Phase II will also inform our need for additional data in support of an initial FDA clearance as a device for the monitoring of SLE disease activity. The application being developed in this proposal will enable early detection of a flare state, optimize SLE phenotype- and severity- specific treatment for maximum disease response, facilitate early treatment intervention to minimize the risk of organ damage, and has the potential to be used as a clinical trial endpoint for the development of new SLE therapeutics.