ZINC THERAPY FOR SCLERODERMA--PHASE I STUDY

锌疗法治疗硬皮病——第一阶段研究

• 批准号: 6121422
• 负责人: FREDRICK M WIGLEY
• 金额: $ 6.52万
• 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: 1998-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6121422
• 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 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.

目前还没有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修饰以及成纤维细胞胶原蛋白过量产生与该疾病的发病机制有关。锌已在体外显示出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，特别是威尔逊病，但锌治疗硬皮病患者的安全性仍有待确定。本研究的目的是评估口服硫酸锌在硬皮病患者中的安全性和生物利用度。使用威尔逊病治疗常见的给药方案，在为期6周的试验中，对弥漫性硬皮病患者的不良事件进行临床监测，作为主要研究结果。6例患者入组研究。无显著不良事件，无方案脱落。血清锌水平从79.6+/-11.2 μ g/dl（平均值+/-标准差）增加到129.6 +/- 35.1 μ g/dl，具有统计学显著性差异（Student 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。锌治疗组患者和医生总体视觉模拟量表评分、健康评估问卷评分和改良Rodnan皮肤评分均有所改善，但未达到统计学显著性。6名患者中有3名在研究方案结束时选择继续服用锌，因为主观感觉有益。本研究的结果表明，锌治疗硬皮病患者是安全和生物利用度。一项II期临床试验，以评估锌治疗硬皮病的临床效益是必要的。