Clinical Trial: A Pilot Study to Evaluate the Safety and Efficacy of Oral Treprostinil in the Treatment of Calcinosis in Patients With Systemic Sclerosis
Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional
Official Title: A Pilot Study to Evaluate the Safety and Efficacy of Oral Treprostinil in the Treatment of Calcinosis in Patients With Systemic Sclerosis
Brief Summary: This is a prospective open-label trial that will enroll 12 patients with systemic sclerosis (SSc) and at least one calcinotic lesion of the hands that is palpable on physical examination and also measureable on hand radiographs, at one single center. Each subject will receive treprostinil orally for 12 months, and follow-up evaluations will be performed every 3 months. Our main objective is to determine whether oral treprostinil is safe, and effective in reducing calcinosis in patients with SSc. We hypothesize that calcinosis is a result of microvascular injury and ischemic damage, and that therefore treprostinil may be beneficial in the treatment of calcinosis in patients with SSc.
Detailed Summary:
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Background:
Calcinosis cutis is the deposition of calcium in the skin and subcutaneous tissues. It is a common and potentially debilitating manifestation of systemic sclerosis (SSc), affecting almost one quarter of these patients. Several studies have found an association between calcinosis and vascular manifestations of SSc including digital ulcers (DU), and acro-osteolysis. The investigators confirmed this in a retrospective multi-center international cohort study of 5280 patients with SSc where DUs were the strongest predictor of calcinosis in multivariate analysis (OR 3.7, 95%CI 2.6-5.3, p<0.0001).
Treprostinil delivered by continuous subcutaneous infusion was effective in both the healing and prevention of DU in patients with SSc in an open-label, single-center clinical trial of 5 (of 12) patients who were able to tolerate the medication. A study of 148 subjects with DU showed that the administration of oral treprostinil up to 16 mg twice daily for 20 weeks was associated with a small but statistically insignificant reduction in net ulcer burden in comparison to placebo. Additionally, preliminary observations in the Pulmonary Hypertension Assessment and Recognition of Outcomes in Scleroderma (PHAROS) registry have found that two patients with SSc-PAH and calcinosis treated with subcutaneous treprostinil for PAH experienced approximately 50% radiographic improvement in their calcinosis lesions after 6 months of therapy.
The investigators developed and validated a novel radiographic scoring system to assess the severity of calcinosis affecting the hands of patients with SSc that accounts for area coverage, density, and anatomic location. This scoring system is feasible and was found to have
Sponsor: Stanford University
Current Primary Outcome:
- To assess the number of participants with treatment-related adverse events following treatment with oral treprostinil [ Time Frame: 12 months ]
- To determine the mean rate of change of calcinosis in radiograph following treatment with oral treprostinil as assessed by a novel radiographic scoring system [ Time Frame: 12 months ]
Original Primary Outcome: Same as current
Current Secondary Outcome:
- To assess the effect of oral treprostinil on the change in Scleroderma Health Assessment Questionnaire (SHAQ) [ Time Frame: 12 months ]
- To assess the effect of oral treprostinil on the change in Cochin Hand Functional Scale [ Time Frame: 12 months ]
- To assess the effect of oral treprostinil on the change in SF-36 [ Time Frame: 12 months ]
- To assess the effect of oral treprostinil on the change in Mawdsley Calcinosis Questionnaire [ Time Frame: 12 months ]
- To assess the effect of oral treprostinil on the change in Raynaud Condition Score [ Time Frame: 12 months ]
- To assess the effect of oral treprostinil on the change in patient global assessment of calcinosis severity [ Time Frame: 12 months ]
- To assess the effect of oral treprostinil on the change in physician global assessment of calcinosis severity [ Time Frame: 12 months ]
- To assess changes in blood flow using SPY perfusion machine following treatment with treprostinil at 1 year compared to baseline. [ Time Frame: 12 months ]
- To assess the number of patients with changes in vascular and SSc-PAH associated biomarkers following treatment with treprostinil at 1 year compared to baseline [ Time Frame: 12 months ]
Original Secondary Outcome: Same as current
Information By: Stanford University
Dates:
Date Received: January 19, 2016
Date Started: October 2016
Date Completion: December 2018
Last Updated: October 13, 2016
Last Verified: October 2016
