Validating Novel Outcomes to Enable Systemic Sclerosis Calcinosis Cutis Clinical Trials - ABSTRACT: About 40% of patients with systemic sclerosis (SSc) develop calcinosis cutis/calcinosis (painful calcium deposits in the skin), that are a leading cause of physical impairments. Many treatments are currently prescribed including sodium thiosulfate, yet there are no high-quality data to support use of any treatment. Before SSc-calcinosis clinical trials can be conducted, quantitative outcomes to measure change over time are needed. The goal of this proposal is to test the performance of two quantitative outcomes for SSc-calcinosis: the Mawdsley Calcinosis Questionnaire and a quantitative CT imaging outcome for calcinosis. Fifty-six patients will be recruited from the Yale Scleroderma Program, through advertisements posted on three websites: one internal and two external (the National Scleroderma Foundation and the Scleroderma Research Foundation), from colleagues in New York City and Rhode Island, and with mailed advertisements to members of regional rheumatology and dermatology professional societies. Patients with symptomatic calcinosis will be recruited who desire treatment for a calcinosis region of interest (ROI) that they will define. Patients will receive topical or intralesional (according to protocol) sodium thiosulfate, a proposed calcinosis therapy with promising effectiveness data, to ensure that calcinosis change occurs during the study. At baseline, 3-, and 6-months, research participants will complete the Mawdsley Calcinosis Questionnaire (MCQ), a newly developed and partially validated instrument, as well as a calcinosis visual analog scale (VAS). They will undergo CT of the ROI (baseline and 6-months) and calcinosis volume will be quantified using open-source BioImageSuite Web Software developed at our institution. In patients with symptomatic SSc-calcinosis who receive STS treatment for six months, we will test two aims. In Aim 1, we will evaluate the performance of the MCQ as the primary outcome compared to the calcinosis VAS. In Aim 2, we will measure change in the MCQ (or the calcinosis VAS depending upon the performance of the MCQ in Aim 1) compared to quantitative CT imaging outcomes. The results of the present proposal will be used to inform the design of future clinical trials to test the efficacy of sodium thiosulfate and other rationale therapies for calcinosis. This proposal is significant because: 1) calcinosis is a leading cause of decreased health-related quality-of-life in patients living with SSc, 2) no treatment guidelines have been developed to inform medical decision-making because no Phase 3 clinical trials have ever been conducted; 3) quantitative outcomes need to be validated to pave the way to calcinosis clinical trials. The innovation in this proposal lies in: 1) an independent performance evaluation of the MCQ for measurement of the impact of calcinosis on SSc patients’ feel and function and its responsiveness to calcinosis change in patients receiving STS, 2) assessment of our BioImageSuite software for regional and serial quantification of calcinosis on CT. Our team is comprised of SSc, imaging, musculoskeletal radiology and biostatistical experts. The environment is conducive to the successful completion the studies who results will form the basis for the first Phase 3 trial ever conducted for SSc-calcinosis.
