INITIAL THERAPY OF WILSON'S DISEASE

威尔逊病的初始治疗

• 批准号: 6158308
• 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/6158308
• 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 Patients will be withdrawn from the protocol if they manifest neurologic worsening over a two week period of examination or if serious hematologic or biochemical abnormalities occur.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疾病，无论种族如何，每 30,000 人中就有 1 人受到影响。 青霉胺是第一个为治疗这些患者而开发的口服药物，然而，用青霉胺治疗威尔逊病的神经系统表现会导致在治疗初始阶段 10-50% 的神经系统恶化。 虽然许多患者通过继续治疗而康复，但有些患者留下了永久性的严重残疾。 另外两种口服螯合剂已用于治疗威尔逊氏病，即四硫代钼酸盐（TM）（一种正在评估的实验药物）和曲恩汀（一种批准用于青霉胺不耐受患者的替代药物）。 锌是另一种口服药物，通过阻止铜吸收发挥作用，但其起效缓慢，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四硫代钼酸盐（TM）（一种实验性铜螯合剂）与曲恩汀，确定患有威尔逊病神经系统表现的患者的最佳初始治疗模式。 该研究的设计是给患者服用 TM 或曲恩汀以及锌，锌是一种本身会阻止铜吸收但不会直接去除铜储备的药物。 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异常肝功能（如果一开始就存在）的正常化来确定。 在八周的治疗期间，还将通过每周进行的神经系统和言语检查对患者进行临床监测。 每周进行一次血液学和生化筛查；以排除药物毒性。 如果患者在两周的检查期间表现出神经系统恶化或出现严重的血液学或生化异常，则他们将退出该方案。接受这种治疗后，患者将继续接受锌治疗，并每半年或更频繁地根据需要进行监测。 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，并且对该疾病的评估作为研究的一部分完成，要么通过适当的测试被诊断为患有威尔逊氏病并接受青霉胺治疗不到两周。