THERAPY OF WILSONS DISEASE W/ TETRATHIOMOLYBDATE COMPARISON W/ TRIENTINE

四硫代钼酸盐治疗威尔逊病与曲恩汀的比较

• 批准号: 6303500
• 负责人: GEORGE J BREWER
• 金额: $ 0.02万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-12-01 至 2001-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6303500
• 关键词: chelating agents; chelation therapy; clinical research; clinical trials; copper; drug adverse effect; drug screening /evaluation; hepatolenticular degeneration; human subject; human therapy evaluation; liver disorder chemotherapy; longitudinal human study; metal complex; orphan disease /drug; outcomes research

The maintenance therapy of Wilson's disease is now well covered with the recent FDA approval of zinc acetate. However, the initial therapy of patients presenting with neurologic disease is problematic. Zinc is rather slow-acting and the disease of the acutely ill patient may progress prior to zinc controlling copper toxicity. The copper chelator that has been used the longest for Wilson's disease, penicillamine, is extremely dangerous for these patients. The copper chelator, trientine, has seen limited use, but seems to have fewer side effects than penicillamine. Initial worsening has not yet been reported, although it is a theoretical risk with trientine.We have introduced a new orphan drug (tetrathiomolybdate, or TM) for the initial treatment of these patients. TM has ideal properties of fast action, and doesn't cause initial worsening. Here we propose a 3 year, phase III double blind, two site, study comparing TM to trientine for initial therapy of neurologically presenting patients. We project a trial of 90 patients, 45 in each arm. The major questions to be answered are: Is there a difference in the rate of initial neurological deterioration? Is there a difference in degree of neurological recovery at years 1 and 2? Are there differences in the incidence of serious side effects? At the completion of the study, we will not only have answered the questions relating to TM vs. trientine, but we will have characterized the efficacy and toxicity of trientine, a drug already on the market, in the initial treatment setting.

现在，Wilson病的维持疗法已被FDA近期乙酸锌的批准所覆盖。 但是，出现神经系统疾病的患者的初始治疗是有问题的。 锌的作用相当缓慢，并且在控制铜毒性之前，患者的疾病可能会进展。 用于威尔逊氏病最长的铜螯合剂，青霉素对这些患者极为危险。 铜螯合剂Trientine的使用有限，但似乎比青霉素更少。 尽管这是Trientine的理论风险，但尚未报告最初的恶化。我们引入了一种新的孤儿药（Tetrathiomolybdate或TM），用于初步治疗这些患者。 TM具有快速动作的理想特性，并且不会导致初始恶化。在这里，我们提出了一个3年，第三阶段双盲，两个地点，将TM与Trientine进行了研究，以对神经学出现患者进行初步治疗。 我们预测了90名患者的试验，每只手臂为45例。 要回答的主要问题是：初始神经系统恶化的速度是否有差异？ 在1和2年代，神经恢复程度有差异吗？ 严重副作用的发生率是否有差异？ 研究完成后，我们不仅会回答与TM与Trientine有关的问题，而且我们将在最初的治疗环境中表征Trientine的功效和毒性。