INITIAL THERAPY OF WILSON'S DISEASE

威尔逊病的初始治疗

• 批准号: 6295036
• 负责人: MICHAEL L SCHILSKY
• 金额: $ 0.17万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 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/6295036
• 关键词: chelation therapy; clinical research; disease /disorder etiology; drug adverse effect; hepatolenticular degeneration; human subject; human therapy evaluation; molybdenum; nervous system disorder chemotherapy; neurologic manifestations; penicillamine; zinc

Background: Wilson's disease is an autosomal recessive disorder that affects 1 in 30,000 individuals regardless of ethnicity. Penicillamine was the first oral agent developed for treatment of these patients, however treatment with Penicillamine for neurologic manifestations of Wilson's disease causes neurologic worsening in 10-50% during the initial phase of treatment. While many recover with continued treatment, some patients are left with permanent severe disabilities. Two other oral chelating agents have been utilized for treatment of Wilson's disease, tetrathiomolybdate (TM), an experimental drug under evaluation, and Trientine, an alternative agent approved for use in Penicillamine intolerant patients. Zinc is another oral agent that acts by blocking copper absorption, however its onset of action is slow and therefore is less likely to be efficacious in the initial phase of treatment. Study Objective: The objective of the study is to determine the best initial mode of therapy for patients with neurologic manifestations of Wilson's disease by comparing tetrathiomolybdate (TM), an experimental copper-chelator with Trientine. The design of the study is to give patients either TM or trientine along with zinc, an agent that itself blocks copper absorption but does not directly remove copper stores. The effectiveness of these regimens will be determined biochemically by monitoring for reductions in non-ceruloplasmin bound copper and in urine copper excretion, and for normalization of abnormal liver functions if present at the outset. Patients will also be monitored clinically by neurologic and speech examinations performed on a weekly basis for the eight weeks of treatment. Hematologic and biochemical screening will be performed weekly; to exclude drug toxicity. Patients will be withdrawn from the protocol if they manifest neurologic worsening over a two week period of examination or if serious hematologic or biochemical abnormalities occur. Following this treatment, patients will be maintained on zinc therapy and monitored biannually or more frequently as necessary. Patients to be enrolled in this study will either have been suspected of having Wilson's disease as the etiology of their neurologic disease, and the evaluation for this disorder completed as part of the study, or have been diagnosed as having Wilson's disease with appropriate testing and treated for less than two weeks with Penicillamine.

背景：威尔逊氏病是一种常染色体隐性遗传病，发病率为3万分之一，与种族无关。青霉胺是第一种用于治疗这些患者的口服药物，然而，在治疗的初始阶段，用青霉胺治疗威尔逊氏病的神经系统表现会导致10-50%的神经系统恶化。虽然许多患者通过持续治疗得以康复，但有些患者留下了永久性严重残疾。另外两种口服螯合剂已被用于治疗威尔逊氏病，四硫钼酸盐（TM），一种正在评估的实验性药物，和曲伦汀，一种被批准用于青霉胺不耐患者的替代药物。锌是另一种通过阻断铜的吸收而起作用的口服药物，但其起作用缓慢，因此在治疗的初始阶段不太可能有效。研究目的：本研究的目的是通过比较实验性铜螯合剂四硫钼酸盐（TM）与曲entine，确定具有威尔逊病神经系统表现的患者的最佳初始治疗模式。这项研究的设计是给患者服用TM或曲恩汀和锌，锌本身会阻止铜的吸收，但不会直接去除铜的储存。这些方案的有效性将通过监测非铜蓝蛋白结合铜和尿铜排泄的减少，以及一开始出现的异常肝功能的正常化来确定。在为期八周的治疗中，患者还将接受每周一次的神经和语言检查的临床监测。每周进行血液学和生化筛查；排除药物毒性。如果患者在两周的检查期间出现神经系统恶化或出现严重的血液学或生化异常，将退出方案。在此治疗后，患者将继续接受锌治疗，并根据需要每年监测两次或更频繁。参加本研究的患者要么被怀疑患有威尔逊氏病作为其神经系统疾病的病因，并且该疾病的评估作为研究的一部分完成，要么被诊断患有威尔逊氏病，并通过适当的测试和青霉胺治疗不到两周。