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

在本申请中，我们提出了一种新型医疗器械的初步验证，用于测量系统性 红斑狼疮（SLE）疾病活动。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 患者报告症状。此外，这些生物标志物不能预测爆发状态的发作。 研究表明，管理良好的狼疮患者积累较少的器官损伤， 随着时间的推移，结果会得到改善。对反映疾病的可靠生物标志物的临床需求尚未得到满足 活性以促进特定SLE疾病活性表型和严重程度的治疗。这项措施 有助于指导免疫抑制治疗的充分性或指示需要治疗其他症状。 定期监测这样的终点有可能预测活动的爆发，这将使早期， 预防性干预，改善患者的预后。AlgometRx Inc.，是从儿童国家基金会 医院（CNH）开发和商业化的新技术正在使用的这一建议。这个设备是 非侵入性和无害的神经选择性电刺激与红外线的新型集成 瞳孔测量以激活特定的感觉神经纤维类型，并允许客观量化 感觉神经纤维活性的表征。具体来说，这项技术可以测量SLE的影响， 相关炎症对感觉神经纤维活动的影响。由此产生的SLE指数可以进行比较 在个体内部以及个体之间的测量之间。在这份提案中，我们计划 扩展我们的初步数据，以开发一种易于实施的，非侵入性的和客观的 SLE疾病活动性的生理测量。为此，我们提出以下目标和方法： 目的：建立SLE指数作为SLE疾病活动性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， 疾病活动，每月6至12个月。在每次门诊访视期间，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 SLE指数的可靠性。在对SLEDAI-2K进行初步验证后，我们计划进行第二阶段 该提案将进一步验证该指数，并将促进更大规模的研究，以量化治疗的影响 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 清除作为监测SLE疾病活动的装置。在此开发的应用程序 该提案将能够早期发现病情的发作，优化SLE表型和严重程度特异性治疗 为了最大限度地缓解疾病，促进早期治疗干预，以尽量减少器官损伤的风险， 并且具有用作开发新的SLE治疗剂的临床试验终点的潜力。

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.