ZINC THERAPY FOR SCLERODERMA--PHASE I STUDY

目前还没有已被证明可以改变硬皮病病程的治疗方法，硬皮病是一种中位预期寿命不到10年的疾病。实验证据表明，缺血再灌注诱导的损伤、金属催化的自身抗原结构的改变以及成纤维细胞胶原蛋白的过度产生参与了本病的发病机制。锌在体外被证明可以抑制这些过程中的每一个。锌已被安全地用于治疗其他疾病，特别是威尔逊氏病，但锌疗法在硬皮病患者中的安全性仍有待确定。本研究的目的是评估口服硫酸锌对硬皮病患者的安全性和生物利用度。使用与威尔逊病治疗相同的剂量方案，弥漫性硬皮病患者在为期6周的试验中被作为主要研究结果的不良事件的临床监测。六名患者进入了这项研究。没有重大的不良事件，也没有方案退出。血清锌水平从79.6+/-11.2ug/dl(平均+/-标准差)上升到129.6+/-35.1ug/dl，差异有统计学意义(t检验p=0.0163)。血清锌水平的增加与之前报道的正常受试者的结果一致。患者和医生的全球视觉模拟量表评分、健康评估问卷评分和改良的Rodnan皮肤评分的平均改善在锌治疗后观察到，但没有达到统计学意义。由于主观上的受益感，六名患者中有三名在研究方案结束时选择继续服用锌。本研究结果表明，锌疗法对硬皮病患者是安全和生物有效的。第二阶段试验评估锌治疗硬皮病的临床益处是有必要的。

No treatments exist which have been proven to modify the course of scleroderma, a disease with median life expectancy of less than 10 years. Experimental evidence has implicated ischemia-reperfusion- induced injury, metal-catalyzed modifications of autoantigen structure, and excess fibroblast collagen production in the pathogenesis of this disease. Zinc has been shown in vitro to inhibit each of these processes. Zinc has been used safely for the treatment of other conditions, notably Wilson's Disease, but the safety of zinc therapy in scleroderma patients remains to be established. The aim of this study was to assess the safety and bioavailability of oral zinc sulfate in scleroderma patients. Using a dosing regimen common to Wilson's Disease therapy, patients with diffuse scleroderma were montiored clinically for adverse events as the primary study outcome over a 6-week trial. Six patients entered the study. There were no significant adverse events, and no protocol dropouts. Serum zinc levels increased from 79.6+/- 11.2ug/dl (mean +/- standard deviation) to 129.6 +/- 35.1 ug/dl, a statistically significant difference (Student's t test p=0.0163). This increase in serum zinc levels was consistent with results previously reported for normal subjects. Mean improvements in patient and physician global visual analog scale scores, health assessment questionnaire scores, and modified Rodnan skin scores were observed with zinc therapy, but did not reach statistical significance. Three of the six patients elected to continue taking zinc at the conclusion of the study protocol due to a subjective sense of benefit. The results of this study suggest that zinc therapy is safe and bioavailable in scleroderma patients. A Phase II trial to assess for clinical benefits of zinc therapy in scleroderma is warranted.