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

开发确定系统性红斑狼疮患者生理表型的新技术

• 批准号: 10597545
• 负责人: Julia Cole Finkel
• 金额: $ 27.24万
• 依托单位: ALGOMETRX, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-22 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10597545
• 关键词: Arthritis; Assessment tool; Biological Markers; Child; Clinic; Clinic Visits; Clinical; Clinical Assessment Tool; Clinical Trials; Complement; Complex; Creatinine; Data; Development; Devices; Disease; Early Diagnosis; Early treatment; Electric Stimulation; Enrollment; Exanthema; Fatigue; Fiber; Fibromyalgia; Flare; Hospitals; Immunosuppressive Agents; Individual; Inflammation; Inflammatory; Intervention; Laboratories; Lupus; Measurement; Measures; Mediating; Medical Device; Monitor; Nephritis; Nerve Fibers; Nociception; Organ; Pain; Patient-Focused Outcomes; Patients; Peripheral; Pharmaceutical Preparations; Phase; Phenotype; Physiological; Proteins; Public Health; Pupil; Reporting; Sensitivity and Specificity; Serology; Severities; Specificity; Symptoms; Systemic Lupus Erythematosus; Technology; Testing; Therapeutic; Therapeutic immunosuppression; Time; Urine; Validation; Visit; afferent nerve; anti-dsDNA antibodies; autoreactivity; body system; cytokine; improved; improved outcome; indexing; inflammatory marker; monitoring device; multidisciplinary; new technology; novel; preemptive intervention; response; risk minimization; symptom management; tool

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.

在此应用中，我们建议对一种用于测量全身性的新型医疗设备进行初步验证。 红斑狼疮（SLE）疾病活动性是一种涉及许多器官的复杂炎症性疾病。 现有的用于追踪炎症的评估工具和实验室测试不能可靠地反映。 此外，这些生物标志物无法预测发作状态的发生。 研究表明，狼疮管理良好的患者积累的器官损伤较少，并证明 随着时间的推移，结果得到改善。对反映疾病的可靠生物标志物的临床需求尚未得到满足。 促进治疗特定 SLE 疾病活动表型和严重程度的活性。 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。 定期监测此类终点有可能预测活动的爆发，从而尽早、 AlgometRx Inc. 是从国家儿童医院分拆出来的。 医院 (CNH) 开发并商业化本提案中使用的新技术。 非侵入性、无害的神经选择性电刺激与红外线的新颖整合 瞳孔测量法激活特定的感觉神经纤维类型并允许客观量化 具体来说，该技术测量 SLE- 的影响。 与感觉神经纤维活动相关的炎症 所得的 SLE 指数可以进行比较。 在本提案中，我们计划在个人内部以及个人之间随时间推移采取措施。 扩展我们的初步数据，开发一个易于实施、非侵入性和客观的方法 为了实现这一目标，我们提出以下目标和方法： 目的：建立 SLE 指数的初步验证，作为 SLE 疾病活动的客观衡量标准。 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情况 每月进行 6 至 12 个月的疾病活动 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。 通过评估敏感性、特异性和 在针对 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促进更大规模的研究以量化治疗的影响 II 期试验还将告知我们需要更多数据来支持最初的 FDA 试验。 清除作为监测 SLE 疾病活动的设备。 该提案将能够及早发现耀斑状态，优化 SLE 表型和严重程度的特异性治疗 为了最大限度地提高疾病反应，促进早期治疗干预，以尽量减少器官损伤的风险， 并有潜力用作开发新的 SLE 疗法的临床试验终点。