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

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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.