ZINC THERAPY FOR SCLERODERMA--PHASE I STUDY

锌疗法治疗硬皮病——第一阶段研究

• 批准号: 6281962
• 负责人: FREDRICK M WIGLEY
• 金额: $ 5.69万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-10 至 1998-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6281962
• 关键词: clinical research; clinical trial phase I; dosage; human subject; human therapy evaluation; oral administration; pharmacokinetics; questionnaires; scleroderma; skin disorder chemotherapy; systemic scleroderma; zinc

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 is 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 will be monitored clinically for adverse events as the primary study outcome over a 6-week trial. To date, there have been no significant adverse events, and no prptocol dropouts. Mean increases in serum zinc levels in scleroderma patients have been observed, consistent with those seen in other populations. Two of four patients to complete the study protocol have elected to continue taking zinc at the conclusion of the study protocol due to a subjective sense of benefit. Mean improvements in patient and physician global visual analogue scale scores, health assessment questionnaire scores, and modified Rodnan skin scores have been observed. Measures of cutaneous fibroblast zinc levels before and after zinc therapy are pending. If zinc is safe and bioavailable when administered to scleroderma pateints, it holds promise as an agent which may favorably alter the clinical course of scleroderma.

目前还没有任何治疗方法被证明可以改变 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修饰和过量 成纤维细胞胶原蛋白的产生在这种疾病的发病机制。 锌 已经在体外显示出抑制这些过程中的每一个。锌已 安全用于治疗其他疾病，特别是威尔逊氏病 疾病，但锌治疗硬皮病患者的安全性仍有待进一步研究。 建立。 本研究的目的是评估口服的安全性和生物利用度 硫酸锌在硬皮病患者中的应用。使用常见的给药方案 威尔逊氏病治疗，弥漫性硬皮病患者将 临床监测不良事件作为主要研究结局， 为期六周的审判 到目前为止，还没有重大的不良事件， 辍学生硬皮病患者血清锌水平的平均升高 观察到，与其他人群中观察到的一致。两 完成研究方案的4名患者选择继续 在研究方案结束时由于主观原因服用锌 利益感。患者和医生整体视力的平均改善 模拟量表评分、健康评估问卷评分，以及 已经观察到改良的Rodnan皮肤评分。皮肤测量 锌治疗前后的成纤维细胞锌水平有待确定。如果锌 是安全的和生物可利用的， 作为一种可能有利地改变临床过程的药物， 硬皮病